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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_16 | Pages 36 - 36
19 Aug 2024
Ma C Goodnough LH Zhao L Chow SK Wang Y Chan CKF Goodman SB
Full Access

Bone marrow stem cells (BMSCs) represent a collection of different cell types exhibiting stem cell characteristics but with notable heterogeneity. Among these, Skeletal Stem Cells (SSCs) represent a distinct matrix subgroup within BMSC and demonstrate a specialized capacity to facilitate bone formation, recruit chondrocytes, and contribute to hematopoiesis. SSCs play a pivotal role in orchestrating the functions of skeletal organs. Local ischemia has a significant impact on cell survival and function. We hypothesize that bone ischemia induces alterations in the differentiation potential of SSCs, consequently influencing changes in bone structure.

We mechanically dissected tissue from the necrotic segment in the femoral head and more normal appearing areas from the femoral neck of specimens from 5 patients diagnosed with osteonecrosis of the femoral head (ONFH). These tissues were enzymatically broken down into individual cell suspensions. Utilizing fluorescence-activated cell sorting (FACS) based on specific surface markers indicative of human skeletal stem cells (hSSC), namely CD45- CD235a- CD31- TIE2- Podoplanin (PDPN)+ CD146- CD73+ CD164+, we isolated a distinct cell population. Subsequent in vitro evaluations, focusing on clonogenicity, osteogenesis, and chondrogenesis were conducted to assess the functional prowess of these SSCs. Moreover, we introduced BMP2 at a concentration of 50ng/ml to SSCs extracted from necrotic regions to potentially reinstate their osteogenic capabilities.

We effectively isolated SSCs from both Necrotic and Non-necrotic Zones. We observed an augmented clonal formation capacity and chondrogenesis ability of SSCs isolated from the necrotic region, accompanied by a significant decline in osteogenic ability (P<0.01), an effect not reversible even with the addition of BMP2.

Ischemia adversely affects the proliferation and function of SSCs, resulting in a diminished osteogenic capacity and an insensitivity to BMP2, ultimately leading to structural alterations in bone tissue.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 332 - 341
5 Jul 2024
Wang T Yang C Li G Wang Y Ji B Chen Y Zhou H Cao L

Aims

Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI).

Methods

A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR.


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 532 - 539
1 Jun 2024
Lei T Wang Y Li M Hua L

Aims

Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and platelet-rich plasma (PRP). Network meta-analysis allows for comparisons between two or more treatment groups and uses direct and indirect comparisons between interventions. This network meta-analysis aims to compare the efficacy of various IA injections used in the management of hip OA with a follow-up of up to six months.

Methods

This systematic review and network meta-analysis used a Bayesian random-effects model to evaluate the direct and indirect comparisons among all treatment options. PubMed, Web of Science, Clinicaltrial.gov, EMBASE, MEDLINE, and the Cochrane Library were searched from inception to February 2023. Randomized controlled trials (RCTs) which evaluate the efficacy of HA, PRP, local anaesthetic, steroid, steroid+anaesthetic, HA+PRP, and physiological saline injection as a placebo, for patients with hip OA were included.


Aims

In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

Methods

An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD.


Bone & Joint Open
Vol. 5, Issue 3 | Pages 227 - 235
18 Mar 2024
Su Y Wang Y Fang C Tu Y Chang C Kuan F Hsu K Shih C

Aims

The optimal management of posterior malleolar ankle fractures, a prevalent type of ankle trauma, is essential for improved prognosis. However, there remains a debate over the most effective surgical approach, particularly between screw and plate fixation methods. This study aims to investigate the differences in outcomes associated with these fixation techniques.

Methods

We conducted a comprehensive review of clinical trials comparing anteroposterior (A-P) screws, posteroanterior (P-A) screws, and plate fixation. Two investigators validated the data sourced from multiple databases (MEDLINE, EMBASE, and Web of Science). Following PRISMA guidelines, we carried out a network meta-analysis (NMA) using visual analogue scale and American Orthopaedic Foot and Ankle Score (AOFAS) as primary outcomes. Secondary outcomes included range of motion limitations, radiological outcomes, and complication rates.


Bone & Joint Research
Vol. 13, Issue 1 | Pages 4 - 18
2 Jan 2024
Wang Y Wu Z Yan G Li S Zhang Y Li G Wu C

Aims

cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect.

Methods

CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA).


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 71 - 71
2 Jan 2024
Ma S Dubin A Romero L Loud M Salazar A Chu S Klier N Masri S Zhang Y Wang Y Chesler A Wilkinson K Vásquez V Marshall K Patapoutian A
Full Access

Distal arthrogryposis (DA) is a collection of rare developmental disorders characterized by congenital joint contractures. Most arthrogryposis mutations are in muscle- and joint-related genes, and the anatomical defects originate cell-autonomously within the musculoskeletal tissues. However, gain-of-function (GOF) mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 via unknown mechanisms. We show that expression of a GOF PIEZO2 mutation in proprioceptive sensory neurons mainly innervating muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. Overactive PIEZO2 causes anatomical defects via increased activity within the peripheral nervous system during postnatal development. Surprisingly, overactive PIEZO2 is likely to cause joint abnormalities via increased exocytosis from sensory neuron endings without involving motor circuitry. This reveals a role for somatosensory neurons: excessive mechanosensation within these neurons disrupts musculoskeletal development. We also present proof-of-concept that Botox injection or dietary treatment can counteract the effect of overactive PIEZO2 function to evade DA-like phenotypes in mice when applied during a developmental critical period. These approaches might have clinical applications. Beyond this, our findings call attention to the importance of considering sensory mechanotransduction when diagnosing and treating other musculoskeletal disorders.

Acknowledgements: Our work is supported by National Institutes of Health grant (R35 NS105067, R01 DE022358, R25 SC3GM127195, R25 GM07138, R01GM133845, intramural) and Howard Hughes Medical Institute.


Bone & Joint Research
Vol. 12, Issue 12 | Pages 722 - 733
6 Dec 2023
Fu T Chen W Wang Y Chang C Lin T Wong C

Aims

Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration.

Methods

A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials – acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC – were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 559 - 570
14 Sep 2023
Wang Y Li G Ji B Xu B Zhang X Maimaitiyiming A Cao L

Aims

To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA).

Methods

The data from 348 patients who had RA or osteoarthritis (OA) and had previously undergone a total knee (TKA) and/or a total hip arthroplasty (THA) (including RA-PJI: 60 cases, RA-non-PJI: 80 cases; OA-PJI: 104 cases, OA-non-PJI: 104 cases) were retrospectively analyzed. A receiver operating characteristic curve was used to determine the optimal thresholds of the CRP, ESR, synovial fluid white blood cell count (WBC), and polymorphonuclear neutrophil percentage (PMN%) for diagnosing RA-PJI and OA-PJI. The diagnostic efficacy was evaluated by comparing the area under the curve (AUC) of each index and applying the results of the combined index diagnostic test.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 522 - 535
4 Sep 2023
Zhang G Li L Luo Z Zhang C Wang Y Kang X

Aims

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Methods

The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.


Bone & Joint Research
Vol. 12, Issue 7 | Pages 433 - 446
7 Jul 2023
Guo L Guo H Zhang Y Chen Z Sun J Wu G Wang Y Zhang Y Wei X Li P

Aims

To explore the novel molecular mechanisms of histone deacetylase 4 (HDAC4) in chondrocytes via RNA sequencing (RNA-seq) analysis.

Methods

Empty adenovirus (EP) and a HDAC4 overexpression adenovirus were transfected into cultured human chondrocytes. The cell survival rate was examined by real-time cell analysis (RTCA) and EdU and flow cytometry assays. Cell biofunction was detected by Western blotting. The expression profiles of messenger RNAs (mRNAs) in the EP and HDAC4 transfection groups were assessed using whole-transcriptome sequencing (RNA-seq). Volcano plot, Gene Ontology, and pathway analyses were performed to identify differentially expressed genes (DEGs). For verification of the results, the A289E/S246/467/632 A sites of HDAC4 were mutated to enhance the function of HDAC4 by increasing HDAC4 expression in the nucleus. RNA-seq was performed to identify the molecular mechanism of HDAC4 in chondrocytes. Finally, the top ten DEGs associated with ribosomes were verified by quantitative polymerase chain reaction (QPCR) in chondrocytes, and the top gene was verified both in vitro and in vivo.


Bone & Joint Research
Vol. 12, Issue 7 | Pages 423 - 432
6 Jul 2023
Xie H Wang N He H Yang Z Wu J Yang T Wang Y

Aims

Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture).

Methods

PubMed, Embase, and Cochrane Library were systematically searched to retrieve relevant articles published before 15 November 2022. Studies focusing on the correlation between selenium and BMD, OP, or fracture were included. Effect sizes included regression coefficient (β), weighted mean difference (WMD), and odds ratio (OR). According to heterogeneity, the fixed-effect or random-effect model was used to assess the association between selenium and bone health.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_12 | Pages 73 - 73
23 Jun 2023
Sheth N Bostrom M Winzenrieth R Humbert L Pearman L Caminis J Wang Y Boxberger J Krohn K
Full Access

To evaluate the effects of 6 and 18 months of abaloparatide (ABL) compared with placebo (PBO) on bone mineral density (BMD) in the acetabular regions of postmenopausal women with osteoporosis (OP).

Acetabular bone loss, as may occur in OP, increases risk of acetabular fragility fracturesa. In total hip arthroplasty (THA), low acetabular BMD adversely affects primary stability, osseointegration, and migration of acetabular cups.c ABL is an osteoanabolic agent for the treatment of men and postmenopausal women with OP at high risk for fracture. Effects of ABL on acetabular BMD are unknown.

Hip DXA scans were obtained at baseline, 6, and 18 months from a random subgroup of postmenopausal women (aged 49–86 y) from the phase 3 ACTIVE trial randomized to either ABL 80 µg/d or PBO (n=250/group). Anatomical landmarks were identified in each DXA scan to virtually place a hemispherical shell model of an acetabular cup and define regions of interest corresponding to DeLee & Charnley zones 1 (R1), 2 (R2), and 3 (R3). BMD changes compared to baseline were calculated for each zone. Statistical P values were based on a repeated mixed measures model.

BMD in all zones were similar at baseline in the ABL and PBO groups. BMD significantly increased in the ABL group at 6 and 18 months compared with PBO (all P<0.0001 vs PBO). BMD in the PBO group was relatively stable over time.

ABL treatment resulted in rapid and progressive increases in BMD of all 3 acetabular zones. Increasing acetabular BMD has the potential to improve acetabular strength, which may reduce risk of acetabular fragility fractures. In bone health optimization prior to THA, increased acetabular BMD via ABL may provide better primary stability and longevity of acetabular cups in postmenopausal women with OP.


Bone & Joint Research
Vol. 12, Issue 4 | Pages 259 - 273
6 Apr 2023
Lu R Wang Y Qu Y Wang S Peng C You H Zhu W Chen A

Aims

Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism.

Methods

In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 76 - 76
4 Apr 2023
LU X BAI S LIN Y YAN L LI L WANG M JIANG Z WANG H YANG B YANG Z WANG Y FENG L JIANG X PONOMAREV E LEE W LIN S KO H LI G
Full Access

Based on Ilizarov's law of tension-stress principle, distraction histogenesis technique has been widely applied in orthopaedic surgery for decades. Derived from this technique, cranial bone transport technique was mainly used for treating cranial deformities and calvarial defects. Recent studies reported that there are dense short vascular connections between skull marrow and meninges for immune cells trafficking, highlighting complex and tight association between skull and brain. Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia without effective therapy. Meningeal lymphatics have been recognized as an important mediator in neurological diseases. The augmentation of meningeal lymphatic drainage might be a promising therapeutic target for AD. Our proof-of-concept study has indicated that cranial bone transport can promote ischemic stroke recovery via modulating meningeal lymphatic drainage function, providing a rationale for treating AD using cranial bone maneuver (CBM). This study aims to investigate the effects of CBM on AD and to further explore the potential mechanisms.

Transgenic 5xFAD mice model was used in this study. After osteotomy, a bone flap was used to perform CBM without damaging the dura. Open filed test, novel object recognition test and Barn's maze test were used to evaluate neurological functions of 5xFAD mice after CBM treatment. Congo red and immunofluorescence staining were used to evaluate amyloid depositions and Aβ plaques in different brain regions. Lymphangiogenesis and the level of VEGF-C were examined after CBM treatment. OVA-A647 was intra-cisterna-magna injected to evaluate meningeal lymphatic drainage function after CBM treatment.

CBM significantly improved memory functions and reduced amyloid depositions and Aβ plaques in the hippocampus of 5xFAD mice. A significant increase of meningeal lymphatic vessels in superior sagittal sinus and transverse sinus, and the upregulation of VEGF-C in meninges were observed in 5xFAD mice treated with CBM. Moreover, CBM remarkably enhanced meningeal lymphatic drainage function in 5xFAD mice (n=5-16 mice/group for all studies).

CBM may promote meningeal lymphangiogenesis and lymphatic drainage function through VEGF-C-VEGFR3 pathway, and further reduce amyloid depositions and Aβ plaques and alleviate memory deficits in AD.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 24 - 24
4 Apr 2023
Randolph M Guastaldi F Fan Y Yu R Wang Y Farinelli W Redmond R
Full Access

Lesions in the joint surface are commonly treated with osteoarticular autograft transfer system (OATS), autologous cell implantation (ACI/MACI), or microfracture. Tissue formed buy the latter commonly results in mechanically inferior fibrocartilage that fails to integrate with the surrounding native cartilage, rather than durable hyaline cartilage. Fractional laser treatment to make sub-millimeter (<500 µm) channels has been employed for tissue regeneration in the skin to facilitate rejuvenation without typical scarring. Additionally, we have pioneered a means to generate articular cartilage matrix from chondrocytes—dynamic Self-Regenerating Cartilage (dSRC). Combining these two approaches by performing fractional laser treatment of the joint cartilage and treating with dSRC is a new paradigm for joint surface restoration. This approach was refined in a series of in vitro experiments and tested in swine knee defects during a 6-month study in 12 swine.

dSRC are generated by placing 107 swine knee chondrocytes into sealed 15-mL polypropylene tubes and cultured on a rocker at 40 cycles per minute for 14 days at 37°C. The chondrocytes aggregate and generate new extracellular matrix to form a pellet of dSRC. Channels of approximately 300-500 µm diameter were created by infrared laser ablation in swine cartilage (in vitro) and swine knees (in vivo). The diameter and depth of the ablated channel in the cartilage was controlled by the light delivery parameters (power, spot size, pulse duration) from a fractional 2.94 µm Erbium laser. The specimens were evaluated with histology (H&E, safranin O, toluidine blue) and polarized-sensitive optical coherence tomography for collagen orientation.

We can consistently create laser-ablated channels in the swine knee and successfully implant new cartilage from dSRC to generate typical hyaline cartilage in terms of morphology and biochemical properties. The neocartilage integrates with host cartilage in vivo.

These findings demonstrate our novel combinatorial approach for articular cartilage rejuvenation.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 56 - 56
4 Apr 2023
Sun Y Zheng H Kong D Yin M Chen J Lin Y Ma X Tian Y Wang Y
Full Access

Using deep learning and image processing technology, a standardized automatic quantitative analysis systerm of lumbar disc degeneration based on T2MRI is proposed to help doctors evaluate the prognosis of intervertebral disc (IVD) degeneration.

A semantic segmentation network BianqueNet with self-attention mechanism skip connection module and deep feature extraction module is proposed to achieve high-precision segmentation of intervertebral disc related areas. A quantitative method is proposed to calculate the signal intensity difference (SI) in IVD, average disc height (DH), disc height index (DHI), and disc height-to-diameter ratio (DHR). According to the correlation analysis results of the degeneration characteristic parameters of IVDs, 1051 MRI images from four hospitals were collected to establish the quantitative ranges for these IVD parameters in larger population around China.

The average dice coefficients of the proposed segmentation network for vertebral bodies and intervertebral discs are 97.04% and 94.76%, respectively. The designed parameters of intervertebral disc degeneration have a significant negative correlation with the Modified Pfirrmann Grade. This procedure is suitable for different MRI centers and different resolution of lumbar spine T2MRI (ICC=.874~.958). Among them, the standard of intervertebral disc signal intensity degeneration has excellent reliability according to the modified Pfirrmann Grade (macroF1=90.63%~92.02%).

we developed a fully automated deep learning-based lumbar spine segmentation network, which demonstrated strong versatility and high reliability to assist residents on IVD degeneration grading by means of IVD degeneration quantitation.


The Bone & Joint Journal
Vol. 104-B, Issue 7 | Pages 867 - 874
1 Jul 2022
Ji B Li G Zhang X Xu B Wang Y Chen Y Cao L

Aims

Periprosthetic joint infections (PJIs) with prior multiple failed surgery for reinfection represent a huge challenge for surgeons because of poor vascular supply and biofilm formation. This study aims to determine the results of single-stage revision using intra-articular antibiotic infusion in treating this condition.

Methods

A retrospective analysis included 78 PJI patients (29 hips; 49 knees) who had undergone multiple prior surgical interventions. Our cohort was treated with single-stage revision using a supplementary intra-articular antibiotic infusion. Of these 78 patients, 59 had undergone more than two prior failed debridement and implant retentions, 12 patients had a failed arthroplasty resection, three hips had previously undergone failed two-stage revision, and four had a failed one-stage revision before their single-stage revision. Previous failure was defined as infection recurrence requiring surgical intervention. Besides intravenous pathogen-sensitive agents, an intra-articular infusion of vancomycin, imipenem, or voriconazole was performed postoperatively. The antibiotic solution was soaked into the joint for 24 hours for a mean of 16 days (12 to 21), then extracted before next injection. Recurrence of infection and clinical outcomes were evaluated.


Bone & Joint Research
Vol. 11, Issue 1 | Pages 40 - 48
27 Jan 2022
Liao W Sun J Wang Y He Y Su K Lu Y Liao G Sun Y

Aims

In the repair of condylar cartilage injury, synovium-derived mesenchymal stem cells (SMSCs) migrate to an injured site and differentiate into cartilage. This study aimed to confirm that histone deacetylase (HDAC) inhibitors, which alleviate arthritis, can improve chondrogenesis inhibited by IL-1β, and to explore its mechanism.

Methods

SMSCs were isolated from synovium specimens of patients undergoing temporomandibular joint (TMJ) surgery. Chondrogenic differentiation potential of SMSCs was evaluated in vitro in the control, IL-1β stimulation, and IL-1β stimulation with HDAC inhibitors groups. The effect of HDAC inhibitors on the synovium and condylar cartilage in a rat TMJ arthritis model was evaluated.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 142 - 142
1 Nov 2021
Negri S Wang Y Lee S Qin Q Cherief M Hsu GC Xu J Tower RJ Levi B Levin A James A
Full Access

Introduction and Objective

Heterotopic ossification is the formation of extraskeletal mineralized tissue commonly associated with either trauma or surgery. While several mouse models have been developed to better characterize the pathologic progression of HO, no model currently exists to study HO of the hip, the most common location of acquired HO in patients. Owing to the unique biological mechanisms underpinning the formation of HO in different tissues, we sought to develop a model to study the post-surgical HO of the hip.

Materials and Methods

Wild-type mice C57BL/6J mice were used to study the procedure outcomes, while Pdgfra-CreERT2;mT/mG and Scx-GFP reporter animals were used for the lineage tracing experiments (total n=16 animals, male, 12 weeks old). An anterolateral approach to the hip was performed. Briefly, a 2 cm incision was made centered on the great trochanter and directed proximal to the iliac crest and distally over the lateral shaft of the femur. The joint was then reached following the intermuscular plane between the rectus femoris and gluteus medius muscles. After the joint was exposed, the articular cartilage was removed using a micropower drill with a 1.2 mm reamer. The medius gluteus and superficial fascia were then re-approximated with Vicryl 5-0 suture (Ethicon Inc, Somerville, NJ) and skin was then closed with Ethilon 5-0 suture (Ethicon Inc). Live high resolution XR imaging was performed every 2 wks to assess the skeletal tissues (Faxitron Bioptics, Tucson, AZ). The images were then scored using the Brooker classification. Ex-vivo microCT was conducted using a Skyscan 1275 scanner (Bruker-MicroCT, Kontich, Belgium). 3D reconstruction and analysis was performed using Dragonfly (ORS Inc., Montreal, Canada). For the histological analysis of specimens, Hematoxylin and Eosin (H&E), modified Goldner's Trichrome (GMT) stainings were performed. Reporter activity was assessed using fluorescent imaging.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 445 - 458
7 Jul 2021
Zhu S Zhang X Chen X Wang Y Li S Qian W

Aims

The value of core decompression (CD) in the treatment of osteonecrosis of the femoral head (ONFH) remains controversial. We conducted a systematic review and meta-analysis to evaluate whether CD combined with other treatments could improve the clinical and radiological outcomes of ONFH patients compared with CD alone.

Methods

We searched the PubMed, Embase, Web of Science, and Cochrane Library databases until June 2020. All randomized controlled trials (RCTs) and clinical controlled trials (CCTs) comparing CD alone and CD combined with other measures (CD + cell therapy, CD + bone grafting, CD + porous tantalum rod, etc.) for the treatment of ONFH were considered eligible for inclusion. The primary outcomes of interest were Harris Hip Score (HHS), ONFH stage progression, structural failure (collapse) of the femoral head, and conversion to total hip arthroplasty (THA). The pooled data were analyzed using Review Manager 5.3 software.


Bone & Joint Research
Vol. 10, Issue 3 | Pages 203 - 217
1 Mar 2021
Wang Y Yin M Zhu S Chen X Zhou H Qian W

Patient-reported outcome measures (PROMs) are being used increasingly in total knee arthroplasty (TKA). We conducted a systematic review aimed at identifying psychometrically sound PROMs by appraising their measurement properties. Studies concerning the development and/or evaluation of the measurement properties of PROMs used in a TKA population were systematically retrieved via PubMed, Web of Science, Embase, and Scopus. Ratings for methodological quality and measurement properties were conducted according to updated COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. Of the 155 articles on 34 instruments included, nine PROMs met the minimum requirements for psychometric validation and can be recommended to use as measures of TKA outcome: Oxford Knee Score (OKS); OKS–Activity and Participation Questionnaire (OKS-APQ); 12-item short form Knee Injury and Osteoarthritis Outcome (KOOS-12); KOOS Physical function Short form (KOOS-PS); Western Ontario and McMaster Universities Arthritis Index-Total Knee Replacement function short form (WOMAC-TKR); Lower Extremity Functional Scale (LEFS); Forgotten Joint Score (FJS); Patient’s Knee Implant Performance (PKIP); and University of California Los Angeles (UCLA) activity score. The pain and function subscales in WOMAC, as well as the pain, function, and quality of life subscales in KOOS, were validated psychometrically as standalone subscales instead of as whole instruments. However, none of the included PROMs have been validated for all measurement properties. Thus, further studies are still warranted to evaluate those PROMs. Use of the other 25 scales and subscales should be tempered until further studies validate their measurement properties.

Cite this article: Bone Joint Res 2021;10(3):203–217.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 675 - 688
1 Oct 2020
Shao L Gou Y Fang J Hu Y Lian Q Zhang Y Wang Y Tian F Zhang L

Aims

Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process.

Methods

Collagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 μg/kg/day or 40 μg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 701 - 708
1 Oct 2020
Chen X Li H Zhu S Wang Y Qian W

Aims

The diagnosis of periprosthetic joint infection (PJI) has always been challenging. Recently, D-dimer has become a promising biomarker in diagnosing PJI. However, there is controversy regarding its diagnostic value. We aim to investigate the diagnostic value of D-dimer in comparison to ESR and CRP.

Methods

PubMed, Embase, and the Cochrane Library were searched in February 2020 to identify articles reporting on the diagnostic value of D-dimer on PJI. Pooled analysis was conducted to investigate the diagnostic value of D-dimer, CRP, and ESR.


The Bone & Joint Journal
Vol. 102-B, Issue 3 | Pages 336 - 344
1 Mar 2020
Ji B Li G Zhang X Wang Y Mu W Cao L

Aims

In the absence of an identified organism, single-stage revision is contraindicated in prosthetic joint infection (PJI). However, no studies have examined the use of intra-articular antibiotics in combination with single-stage revision in these cases. In this study, we present the results of single-stage revision using intra-articular antibiotic infusion for treating culture-negative (CN) PJI.

Methods

A retrospective analysis between 2009 and 2016 included 51 patients with CN PJI who underwent single-stage revision using intra-articular antibiotic infusion; these were compared with 192 culture-positive (CP) patients. CN patients were treated according to a protocol including intravenous vancomycin and a direct intra-articular infusion of imipenem and vancomycin alternately used in the morning and afternoon. In the CP patients, pathogen-sensitive intravenous (IV) antibiotics were administered for a mean of 16 days (12 to 21), and for resistant cases, additional intra-articular antibiotics were used. The infection healing rate, Harris Hip Score (HHS), and Hospital for Special Surgery (HSS) knee score were compared between CN and CP groups.


The Bone & Joint Journal
Vol. 101-B, Issue 11 | Pages 1438 - 1446
1 Nov 2019
Kong X Chai W Chen J Yan C Shi L Wang Y

Aims

This study aimed to explore whether intraoperative nerve monitoring can identify risk factors and reduce the incidence of nerve injury in patients with high-riding developmental dysplasia.

Patients and Methods

We conducted a historical controlled study of patients with unilateral Crowe IV developmental dysplasia of the hip (DDH). Between October 2016 and October 2017, intraoperative nerve monitoring of the femoral and sciatic nerves was applied in total hip arthroplasty (THA). A neuromonitoring technician was employed to monitor nerve function and inform the surgeon of ongoing changes in a timely manner. Patients who did not have intraoperative nerve monitoring between September 2015 and October 2016 were selected as the control group. All the surgeries were performed by one surgeon. Demographics and clinical data were analyzed. A total of 35 patients in the monitoring group (ten male, 25 female; mean age 37.1 years (20 to 46)) and 56 patients in the control group (13 male, 43 female; mean age 37.9 years (23 to 52)) were enrolled. The mean follow-up of all patients was 13.1 months (10 to 15).


Bone & Joint Research
Vol. 8, Issue 8 | Pages 357 - 366
1 Aug 2019
Zhang B Sun H Zhan Y He Q Zhu Y Wang Y Luo C

Objectives

CT-based three-column classification (TCC) has been widely used in the treatment of tibial plateau fractures (TPFs). In its updated version (updated three-column concept, uTCC), a fracture morphology-based injury mechanism was proposed for effective treatment guidance. In this study, the injury mechanism of TPFs is further explained, and its inter- and intraobserver reliability is evaluated to perfect the uTCC.

Methods

The radiological images of 90 consecutive TPF patients were collected. A total of 47 men (52.2%) and 43 women (47.8%) with a mean age of 49.8 years (sd 12.4; 17 to 77) were enrolled in our study. Among them, 57 fractures were on the left side (63.3%) and 33 were on the right side (36.7%); no bilateral fracture existed. Four observers were chosen to classify or estimate independently these randomized cases according to the Schatzker classification, TCC, and injury mechanism. With two rounds of evaluation, the kappa values were calculated to estimate the inter- and intrareliability.


The Bone & Joint Journal
Vol. 101-B, Issue 4 | Pages 396 - 402
1 Apr 2019
Ji B Wahafu T Li G Zhang X Wang Y Momin M Cao L

Aims

Single-stage revision is not widely pursued due to restrictive inclusion criteria. In this study, we evaluated the results of single-stage revision of chronically infected total hip arthroplasty (THA) using broad inclusion criteria and cementless implants.

Patients and Methods

Between 2010 and 2016, 126 patients underwent routine single-stage revision with cementless reconstruction with powdered vancomycin or imipenem poured into the medullary cavity and re-implantation of cementless components. For patients with a culture-negative hip, fungal infections, and multidrug-resistant organisms, a direct intra-articular infusion of pathogen-sensitive antibiotics was performed postoperatively. Recurrence of infection and clinical outcomes were evaluated. Three patients died and 12 patients (none with known recurrent infection) were lost to follow-up. There were 111 remaining patients (60 male, 51 female) with a mean age of 58.7 (sd 12.7; 20 to 79).


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_13 | Pages 55 - 55
1 Oct 2018
Tibbo ME Wyles CC Maradit-Kremers H Fu S Wang Y Sohn S Berry DJ Lewallen DG
Full Access

Introduction

Manual chart review is labor-intensive and requires specialized knowledge possessed by highly-trained medical professionals. The cost and infrastructure challenges required to implement this is prohibitive for most hospitals. Natural language processing (NLP) tools are distinctive in their ability to extract critical information from raw text in the electronic health records (EHR). As a simple proof-of-concept, for the potential application of this technology, we examined its ability to discriminate between a binary classification (periprosthetic fracture [PPFFx] vs. no PPFFx) followed by a more complex classification of the same problem (Vancouver).

Methods

PPFFx were identified among all THAs performed at a single academic institution between 1977 and 2015. A training cohort (n = 90 PPFFx) selected randomly by an electronic program was utilized to develop a prototype NLP algorithm and an additional randomly-selected 86 PPFFx were used to further validate the algorithm. Keywords to identify, and subsequently classify, Vancouver type PPFFx about THA were defined. The algorithm was applied to consult and operative notes to evaluate language used by surgeons as a means to predict the correct pathology in the absence of a listed, precise diagnosis (e.g. Vancouver B2). Validation statistics were calculated using manual chart review as the gold standard.


The Bone & Joint Journal
Vol. 100-B, Issue 6 | Pages 798 - 805
1 Jun 2018
Zhang Y Guo W Tang X Yang R Ji T Yang Y Wang Y Wei R

Aims

The sacrum is frequently invaded by a pelvic tumour. The aim of this study was to review our experience of treating this group of patients and to identify the feasibility of a new surgical classification in the management of these tumours.

Patients and Methods

We reviewed 141 patients who, between 2005 and 2014, had undergone surgical excision of a pelvic tumour with invasion of the sacrum.

In a new classification, pelvisacral (Ps) I, II, and III resections refer to a sagittal osteotomy through the ipsilateral wing of the sacrum, through the sacral midline, or lateral to the contralateral sacral foramina, respectively. A Ps a resection describes a pelvic osteotomy through the ilium and a Ps b resection describes a concurrent resection of the acetabulum with osteotomies performed through the pubis and ischium or the pubic symphysis. Within each type, surgical approaches were standardized to guide resection of the tumour.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_6 | Pages 2 - 2
1 Apr 2018
Wang Y Huang H
Full Access

Introduction

Satisfaction and survival rates after total knee arthroplasty were high according to literatures. However, around 8% of revision surgeries were still noted and almost half of them were early failures, which were most seen in 2 years after primary surgery. This study aimed to find out the factors lead to early failures after total knee arthroplasty.

Materials and Methods

Data were collected based on the National Health Insurance Research Data Base of Taiwan from 1996 to 2010. Primary total knee arthroplasty surgeries were included. Revisional total knee arthroplasty, removal of total knee implant and arthrotomy surgeries registered after primary total knee surgeries are seen as failures.


The Bone & Joint Journal
Vol. 100-B, Issue 4 | Pages 516 - 521
1 Apr 2018
Qian L Jiang C Sun P Xu D Wang Y Fu M Zhong S Ouyang J

Aims

The aim of this study was to compare the peak pull-out force (PPF) of pedicle-lengthening screws (PLS) and traditional pedicle screws (TPS) using instant and cyclic fatigue testing.

Materials and Methods

A total of 60 lumbar vertebrae were divided into six groups: PLS submitted to instant pull-out and fatigue-resistance testing (groups A1 and A2, respectively), TPS submitted to instant pull-out and fatigue-resistance testing (groups B1 and B2, respectively) and PLS augmented with 2 ml polymethylmethacrylate, submitted to instant pull-out and fatigue-resistance testing (groups C1 and C2, respectively). The PPF and normalized PPF (PPFn) for bone mineral density (BMD) were compared within and between all groups.


Bone & Joint Research
Vol. 6, Issue 4 | Pages 245 - 252
1 Apr 2017
Fu M Ye Q Jiang C Qian L Xu D Wang Y Sun P Ouyang J

Objectives

Many studies have investigated the kinematics of the lumbar spine and the morphological features of the lumbar discs. However, the segment-dependent immediate changes of the lumbar intervertebral space height during flexion-extension motion are still unclear. This study examined the changes of intervertebral space height during flexion-extension motion of lumbar specimens.

Methods

First, we validated the accuracy and repeatability of a custom-made mechanical loading equipment set-up. Eight lumbar specimens underwent CT scanning in flexion, neural, and extension positions by using the equipment set-up. The changes in the disc height and distance between adjacent two pedicle screw entry points (DASEP) of the posterior approach at different lumbar levels (L3/4, L4/5 and L5/S1) were examined on three-dimensional lumbar models, which were reconstructed from the CT images.


The Bone & Joint Journal
Vol. 99-B, Issue 2 | Pages 267 - 275
1 Feb 2017
Liang H Ji T Zhang Y Wang Y Guo W

Aims

The aims of this retrospective study were to report the feasibility of using 3D-printing technology for patients with a pelvic tumour who underwent reconstruction.

Patients and Methods

A total of 35 patients underwent resection of a pelvic tumour and reconstruction using 3D-printed endoprostheses between September 2013 and December 2015. According to Enneking’s classification of bone defects, there were three Type I lesions, 12 Type II+III lesions, five Type I+II lesions, two Type I+II+III lesions, ten type I+II+IV lesions and three type I+II+III+IV lesions. A total of three patients underwent reconstruction using an iliac prosthesis, 12 using a standard hemipelvic prosthesis and 20 using a screw-rod connected hemipelvic prosthesis.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_2 | Pages 20 - 20
1 Jan 2017
Pai S Li J Wang Y Lin C Kuo M Lu T
Full Access

Knee ligament injury is one of the most frequent sport injuries and ligament reconstruction has been used to restore the structural stability of the joint. Cycling exercises have been shown to be safe for anterior cruciate ligament (ACL) reconstruction and are thus often prescribed in the rehabilitation of patients after ligament reconstruction. However, whether it is safe for posterior cruciate ligament (PCL) reconstruction remains unclear. Considering the structural roles of the PCL, backward cycling may be more suitable for rehabilitation in PCL reconstruction. However, no study has documented the differences in the effects on the knee kinematics between forward and backward pedaling. Therefore, the current study aimed to measure and compare the arthrokinematics of the tibiofemoral joint between forward and backward pedaling using a biplane fluoroscope-to- computed tomography (CT) registration method.

Eight healthy young adults participated in the current study with informed written consent. Each subject performed forward and backward pedaling with an average resistance of 20 Nm, while the motion of the left knee was monitored simultaneously by a biplane fluoroscope (ALLURA XPER FD, Philips) at 30 fps and a 14-camera stereophotogrammetry system (Vicon, OMG, UK) at 120 Hz. Before the motion experiment, the knee was CT and magnetic resonance scanned, which enabled the reconstruction of the bones and articular cartilage. The bone models were registered to the fluoroscopic images using a volumetric model-based fluoroscopy-to-CT registration method, giving the 3-D poses of the bones. The bone poses were then used to calculate the rigid-body kinematics of the joint and the arthrokinematics of the articular cartilage. In this study, the top dead center of the crank was defined as 0° so forward pedaling sequence would begin from 0° to 360°.

Compared with forward pedaling, for crank angles from 0° to 180°, backward pedaling showed significantly more tibial external rotation. Moreover, both the joint center and contact positions in the lateral compartment were more anterior while the contact positions in the medial compartment was more posterior, during backward pedaling. For crank angles from 180° to 360°, the above-observed phenomena were generally reversed, except for the anterior-posterior component of the contact positions in the medial compartment.

Forward and backward pedaling displayed significant differences in the internal/external rotations while the rotations in the sagittal and frontal planes were similar. Compared with forward cycling, the greater tibial external rotation for crank angles from 0° to 180° during backward pedaling appeared to be the main reason for the more anterior contact positions in the lateral compartment and more posterior contact positions in the medial compartment.

Even though knee angular motions during forward and backward pedaling were largely similar in the sagittal and frontal planes, significant differences existed in the other components with different contact patterns. The current results suggest that different pedaling direction may be used in rehabilitation programs for better treatment outcome in future clinical applications.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 11 - 11
1 Nov 2016
Vachhani K Wang Y Nam D Whyne C
Full Access

Predictable fracture healing fails to occur in 5–10% of cases. This is particularly concerning among individuals with osteoporosis. With an increasing aging population, one in three women and one in five men above the age of 50 experience fragility fractures. As such, there is a critical need for an effective treatment option that could enhance fracture healing in osteoporotic bone. Lithium, the standard treatment for bipolar disorder, has been previously shown to improve fracture healing through modulation of the Wnt/beta-catenin pathway. We optimised the precise oral lithium administration parameters to improve mechanical strength and enhance healing of femoral fractures in healthy rats. A low dose of Lithium (20 mg/kg) administered seven days post fracture for a two week duration improved torsional strength by 46% at four weeks post fracture compared to non-treated animals. Application of lithium to enhance fracture healing in osteoporotic bone would have a significant healthcare impact and requires further study. Aim: To evaluate the efficacy of optimal lithium administration post fracture on quality of fracture healing in a rat osteoporotic model. Hypothesis: Lithium treatment in osteoporotic rats will improve the structural and mechanical properties of the healing bone despite the impaired nature of bone tissue.

Sprague Dawley female rats (∼350 g, age ∼3 months) were bilaterally ovariectomised and maintained for 3 months to establish the osteoporotic phenotype. A unilateral, closed mid-shaft femoral fracture was created using a weight-drop apparatus. At seven days post fracture, the treatment group received 20 mg/kg-wt lithium chloride via oral gavage daily for 14 days. The control group received an equivalent dose of saline. All animals were sacrificed at day 28 and the femurs harvested bilaterally. Treatment efficacy was evaluated based on torsional loading and stereologic analysis.

Lithium treatment positively impacted the healing femurs, with an average yield torque ∼1.25-fold higher than in the saline group (200±36 vs. 163±31 N-mm, p=0.15). Radiographically, the lithium-treated rats had a high level of restored periosteal continuity, larger bridging and intercortical callus at the fracture site. These hallmarks of healing were generally absent in the saline group. The Lithium group had significantly higher total volume (624±32 vs. 568±95 mm3), lower bone volume fraction (41±4 vs. 50±5%) and higher theoretical torsional rigidity (477±50 vs. 357±93 kN-mm2) compared to the saline group. Torsional strength and stereology values were similar for the contralateral femurs of the two groups.

Lithium was found to enhance fracture healing in osteoporotic bone under the dosing regimen optimised in healthy femora. This is promising data as treatment represents an easily translatable pharmacological intervention for fracture healing that may ultimately reduce the healthcare burden of osteoporotic fractures.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 13 - 13
1 Nov 2016
Nam D Wang Y Whetstone H Alman B
Full Access

The T-lymphocyte secreted pro-inflammatory cytokine, interleukin-17F (IL-17F), was found to be a key mediator in the cellular response of the immune system in the early phase of fracture repair but its intracellular signaling processes are currently not known in osteoblasts. The objective of this study was to identify the signaling proteins and crucial gene targets involved in osteoblast activation via IL-17F. It was hypothesised that IL-17F stimulated osteoblast maturation through a novel GSK3beta / beta-catenin independent pathway.

Mouse pre-osteoblast cell line (MC3T3-E1) was used for IL-17F or Wnt3a treatment. Desired proteins were detected using western blot analysis (antibodies: Phospho-GSK-3beta (Tyr 216), Phospho-GSK-3beta (Ser9), Runx2/cbfa1, TRAF6, Act1, p-ERK2, p-JNK and p-MAPK, C/EBP-beta and & delta). Gene-specific siRNAs of mouse IL-17Ra, IL-17Rc and a non-targeting siRNA (control) were utilised. MC3T3-E1 were transfected with IL-17Ra, IL-17Rc or Negative Control and treated with IL-17F. Chromatin Immunoprecipitation (ChIP-qPCR) was used to evaluate the mouse Runx2 P1 promoter region.

IL-17F increased expression of Col1, BSP, Runx2/cbfa1 and osteocalcin in MC3T3-E1 cells. Western blot analysis confirmed expression of known Wnt signaling proteins TRAF6, Act1, p-ERK2, p-JNK and p-MAPK in both IL-17F and Wnt3a treated cultures, including up-regulation of Runx2/cbfa1, a key transcription factor associated with osteoblast differentiation. IL-17F up-regulation of Runx2/cbfa1 appears independent of the Wnt/beta-catenin pathway as phosphorylated GSK-3beta at the Ser9 site was not detected with IL-17F treatment. Despite this, IL-17F treatment still increased expression of Runx2/cbfa1 downstream, lending evidence for a GSK3beta/beta-catenin independent manner of IL-17F stimulated osteogenesis. While IL-17F and Wnt3a both induced expression of C/EBP-delta, only IL-17F treatment induced expression of C/EBP-beta, an upstream transcription factor of Runx2/cbfa1. Further, siRNA knock down of the IL-17 receptors directly decreased Act1, C/EBP-beta and Runx2/cfba1 expression. By ChIP analysis, IL-17F was shown to upregulate C/EBP-beta expression and stimulated its binding to the P1 Promoter of the Runx2/cbfa1 gene.

The C/EBP-beta transcription factor was shown to be a key regulator of early osteogenesis. C/EBP-beta up-regulates Runx2/cbfa1 expression by directly binding to the Runx2/cbfa1 P1 promoter in osteoblasts. C/EBP-beta was activated in the osteoblast by IL-17F but not by Wnt3a adding further support to a novel GSK3beta/beta-catenin independent pathway. Our data shows that IL-17F, a cytokine secreted by T-lymphocytes, stimulates osteoblast maturation through a novel GSK3beta/beta-catenin independent pathway and reveals a crucial interaction between C/EBP-beta and the Runx2/cbfa1 P1 promoter not previously been shown in osteogenesis signaling further.


Bone & Joint Research
Vol. 5, Issue 6 | Pages 276 - 279
1 Jun 2016
Zhu H Gao Y Wang Y Zhang C

Objectives

Circulating exosomes represent novel biomarkers for multiple diseases. In this study, we investigated whether circulating exosome levels could be used as a diagnostic biomarker for steroid-induced osteonecrosis of the femoral head (ONFH).

Methods

We assessed the serum exosome level of 85 patients with steroid-induced ONFH and 115 healthy donors by Nanosight detection. We then assessed the diagnostic accuracy of serum exosomes by receiver operating characteristic curve analysis.


The Bone & Joint Journal
Vol. 98-B, Issue 5 | Pages 672 - 678
1 May 2016
Zhang X Zhang Z Wang J Lu M Hu W Wang Y Wang Y

Aims

The aim of this study is to introduce and investigate the efficacy and feasibility of a new vertebral osteotomy technique, vertebral column decancellation (VCD), for rigid thoracolumbar kyphotic deformity (TLKD) secondary to ankylosing spondylitis (AS).

Patients and Methods

We took 39 patients from between January 2009 and January 2013 (26 male, 13 female, mean age 37.4 years, 28 to 54) with AS and a TLKD who underwent VCD (VCD group) and compared their outcome with 45 patients (31 male, 14 female, mean age 34.8 years, 23 to 47) with AS and TLKD, who underwent pedicle subtraction osteotomy (PSO group), according to the same selection criteria. The technique of VCD was performed at single vertebral level in the thoracolumbar region of AS patients according to classification of AS kyphotic deformity. Pre- and post-operative chin-brow vertical angle (CBVA), sagittal vertical axis (SVA) and sagittal Cobb angle in the thoracolumbar region were reviewed in the VCD and PSO groups. Intra- , post-operative and general complications were analysed in both group.


Bone & Joint Research
Vol. 5, Issue 5 | Pages 169 - 174
1 May 2016
Wang Y Chu M Rong J Xing B Zhu L Zhao Y Zhuang X Jiang L

Objectives

Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations.

Methods

We systematically genotyped rs8044769 and evaluated the association between the genetic variants and OA risk in a case-controlled study including 196 OA cases and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_1 | Pages 118 - 118
1 Jan 2016
Dong N Rickels T Bastian A Wang A Zhou Y Zhang X Wang Y
Full Access

Objective

The purpose of this study was to compare the proximal femoral morphology between normal Chinese and Caucasian populations by 3D analysis derived from CT data.

Materials and Methods

141 anonymous Chinese femoral CT scans (71 male and 70 female) with mean age of 60.1years (range 20–93) and 508 anonymous Caucasian left femoral CT scans (with mean age of 64.8years (range 20–93). The CT scans were segmented and converted to virtual bones using custom CT analytical software. (SOMA™ V.4.0) Femoral Head Offset (FHO) and Femoral Head Position (FHP) were measured from head center to proximal canal central axis and to calcar or 20mm above Lesser Trochanter (LT) respectively. The Femoral neck Anteversion (FA) and Caput-Collum-Diaphyseal (CCD) angles were also measured. The Medial Lateral Widths(MLWn) of femoral canal were measured at 0, -10, LT, -30, -40, -60, -70 and -100mm levels from calcar. Anterior Posterior Widths (APWn) were measured at 0, -60 and -100mm levels. The Flare Index (FI) was derived from the ratio of widths at 0 and -60mmor FI=W0/W−60. All measurements were performed in the same settings for both populations. The comparison was analyzed by Student T test. P<0.05 was considered significant.


The Bone & Joint Journal
Vol. 97-B, Issue 10 | Pages 1405 - 1410
1 Oct 2015
Fu J Song K Zhang YG Zheng GQ Zhang GY Liu C Wang Y

Cardiac disease in patients with ankylosing spondylitis (AS) has previously been studied but not in patients with a kyphosis or in those who have undergone an operation to correct it.

The aim of this study was to measure the post-operative changes in cardiac function of patients with an AS kyphosis after pedicle subtraction osteotomy (PSO).

The original cohort consisted of 39 patients (33 men, six women). Of these, four patients (two men, two women) were lost to follow-up leaving 35 patients (31 men, four women) to study. The mean age of the remaining patients was 37.4 years (22.3 to 47.8) and their mean duration of AS was 17.0 years (4.6 to 26.4). Echocardiographic measurements, resting heart rate (RHR), physical function score (PFS), and full-length standing spinal radiographs were obtained before surgery and at the two-year follow-up.

The mean pre-operative RHR was 80.2 bpm (60.6 to 112.3) which dropped to a mean of 73.7 bpm (60.7 to 90.6) at the two-year follow-up (p = 0.0000). Of 15 patients with normal ventricular function pre-operatively, two developed mild left ventricular diastolic dysfunction (LVDD) at the two-year follow-up. Of 20 patients with mild LVDD pre-operatively only five had this post-operatively. Overall, 15 patients had normal LV diastolic function before their operation and 28 patients had normal LV function at the two-year follow-up.

The clinical improvement was 15 out of 20 (75.0%): cardiac function in patients with AS whose kyphosis was treated by PSO was significantly improved.

Cite this article: Bone Joint J 2015;97-B:1405–10.


The Bone & Joint Journal
Vol. 96-B, Issue 12 | Pages 1586 - 1593
1 Dec 2014
Li H Wang Y Oni JK Qu X Li T Zeng Y Liu F Zhu Z

There have been several studies examining the association between the morphological characteristics seen in acetabular dysplasia and the incidence of the osteoarthritis (OA).

However, most studies focus mainly on acetabular morphological analysis, and few studies have scrutinised the effect of femoral morphology. In this study we enrolled 36 patients with bilateral acetabular dysplasia and early or mid-stage OA in one hip and no OA in the contralateral hip. CT scans were performed from the iliac crest to 2 cm inferior to the tibial tuberosity, and the morphological characteristics of both acetabulum and femur were studied.

In addition, 200 hips in 100 healthy volunteer Chinese adults formed a control group. The results showed that the dysplastic group with OA had a significantly larger femoral neck anteversion and a significantly shorter abductor lever arm than both the dysplastic group without OA and the controls. Femoral neck anteversion had a significant negative correlation with the length of the abductor lever arm and we conclude that it may contribute to the development of OA in dysplastic hips.

Cite this article: Bone Joint J 2014; 96-B:1586–93.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 61 - 61
1 Jul 2014
Alqahtani S Harvey E Henderson J Chodavarapu V Wang Y Allan C
Full Access

Significance

Acute compartment syndrome (ACS) occurs after muscle injury and is characterised by increased pressure in the muscle compartment that can result in devastating complications if not diagnosed and treated appropriately. ACS is currently confirmed by repeated needle sticks to measure the compartment pressure using a hand-held compartment pressure monitor. This approach is often not reproducible and is not appropriate for continuous monitoring. To address the shortcomings of currently available technology we are developing an implantable micro-device that will measure compartment pressure directly and continuously over the 24 hours critical period following injury using a radio frequency identification (RFID) platform integrated with a MEMS capacitive pressure sensor.

Methods

The prototype implantable device measuring 3mmx3mm consists of a capacitive pressure sensor, a sensor readout circuitry, an antenna and a radio frequency reader. A prototype sensor was packaged in Silicone gel (MED-6640, Nusil Technology LLC) for ex vivo and in vivo testing in three compartment models. First, it was tested ex vivo in an airtight vessel using a blood pressure monitor to pump air and increase the pressure inside the vessel. Second, it was implanted in a muscle compartment of a fresh porcine hind limb and an infusion pump with normal saline was used to raise the tissue pressure. Third, it was implanted in the posterior thigh muscle of a rat where the pressure was increased by applying a tourniquet around the thigh. The readings were compared with those from a hand-held Stryker Intra-compartmental Pressure Monitor System used in the trauma room.


The Bone & Joint Journal
Vol. 96-B, Issue 3 | Pages 360 - 365
1 Mar 2014
Zheng GQ Zhang YG Chen JY Wang Y

Few studies have examined the order in which a spinal osteotomy and total hip replacement (THR) are to be performed for patients with ankylosing spondylitis. We have retrospectively reviewed 28 consecutive patients with ankylosing spondylitis who underwent both a spinal osteotomy and a THR from September 2004 to November 2012. In the cohort 22 patients had a spinal osteotomy before a THR (group 1), and six patients had a THR before a spinal osteotomy (group 2). The mean duration of follow-up was 3.5 years (2 to 9). The spinal sagittal Cobb angle of the vertebral osteotomy segment was corrected from a pre-operative kyphosis angle of 32.4 (SD 15.5°) to a post-operative lordosis 29.6 (SD 11.2°) (p < 0.001). Significant improvements in pain, function and range of movement were observed following THR. In group 2, two of six patients had an early anterior dislocation. The spinal osteotomy was performed two weeks after the THR. At follow-up, no hip has required revision in either group. Although this non-comparative study only involved a small number of patients, given our experience, we believe a spinal osteotomy should be performed prior to a THR, unless the deformity is so severe that the procedure cannot be performed.

Cite this article: Bone Joint J 2014;96-B:360–5.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 540 - 540
1 Sep 2012
Wang M Li H Hoey K Hansen E Niedermann B Helming P Wang Y Aras E Schattiger K Bunger C
Full Access

Study design: We conducted a prospective cohort study of 448 patients with a variety of spinal metastases.

Objective

To compare the predictive value of the Tokuhashi scoring system (T12) and its revised edition (T15) for life expectancy both in the entire study group as well as in the various primary tumor subgroups.

Summary of background data

In 1990 Tokuhashi and coworkers formulated a one point-addition-type prognostic scoring system with a total sum of 12 points for preoperative prediction of life expectancy as an adjunct in selecting appropriate treatment. Because the site of the primary tumor influences ultimate survival, the scoring system was revised in 2005 to a total sum of 15 points based on the origin of the primary tumor.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 106 - 106
1 Sep 2012
Xie J Wang Y Yang Z Zhang Y
Full Access

Introduction

To introduce a new classification method and analyze related risk factor about lateral wall perforation associated with lower cervical pedicle screw and free-hand insertion technique.

Methods

A Retrospective study was made to analyze 214 patients (1024 screws) with various cervical spine disorders, involved in pedicle screw instrumentation at C3-7 from July 2004 to July 2009. Researchers assessed the position of the screws in the pedicle by carefully probing intraoperatively and studying postoperative thin-slice computed tomography scan. Perforation of lateral wall was classified into two phases. Phase I refers to the burst of the pedicle by screw, which means that the length of screw threads penetrating the external cortex of pedicles on CT scan is 2 mm, whereas in Phase, the length is >2 mm. The Penetrated screws and related factors were analyzed though Backward Stepwise (Wald) Logistic regression.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 178 - 178
1 Sep 2012
Wang Y Bunger C Hansen E Hoy K Wu C
Full Access

Objective

To identify risk factors for the presence of distal adding-on in Lenke 1A scoliosis and compare different treatment strategies.

Summary of Background Data

Distal adding-on is often accompanied by unsatisfactory clinical outcome and high risk of reoperation. However, very few studies have focused on distal adding-on and its attendant risk factors and optimal treatment strategies remain controversial.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 74 - 74
1 Sep 2012
Wang Y Xiao S Zhang Y Zhang X Wang Z Zheng G
Full Access

Study Design

Retrospective review.

Objective

To report the technique and results of vertebral column decancellation (VCD) for the management of sharp angular spinal deformity.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVII | Pages 36 - 36
1 Jun 2012
Wang Y Bunger C Zhang Y Wu C Hansen E
Full Access

Introduction

How translation of different parts of spine responds to selective thoracic fusion has not been well investigated. Furthermore, how posterior pedicle-screw-only constructs affect spontaneous lumbar curve correction (SLCC) remains unknown. In a retrospective study, we aimed to investigate the balance change after selective thoracic fusion in Lenke 1C type adolescent idiopathic scoliosis (AIS) treated with posterior pedicle-screw-only constructs.

Methods

All AIS cases, surgically treated between 2002 and 2008 in our institute, were reviewed. Inclusion criteria were: patients with Lenke 1C scoliosis treated with posterior pedicle-screw-only constructs; the lowest instrumented vertebra (LIV) ended at L1 level or above; and a minimum 2-year radiographic follow-up. Standing anteroposterior (AP) and lateral digital radiographs from different timepoints (preoperative, immediately postoperative, 3 months postoperative, and final follow-up) were reviewed. In each standing AP radiograph, centre sacral vertical line (CSVL) was drawn first, followed by measurement of the translation (deviation from the CSVL) of some key vertebrae, such as the LIV, LIV+1 (the first vertebra below LIV), LIV+2 (the second vertebra below LIV), LIV+3 (the third vertebra below LIV), lumbar apical vertebra, thoracic apical vertebra, and T1. Additionally, the Cobb angles of major thoracic and lumbar curve were measured at different timepoints, and the correction rate was calculated. Furthermore, clinical photos of patients' back appearance were taken preoperatively and postoperatively.