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Bone & Joint Research
Vol. 13, Issue 7 | Pages 362 - 371
17 Jul 2024
Chang H Liu L Zhang Q Xu G Wang J Chen P Li C Guo X Yang Z Zhang F

Aims

The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA.

Methods

Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database.


Bone & Joint Research
Vol. 12, Issue 11 | Pages 677 - 690
1 Nov 2023
Wang X Jiang W Pan K Tao L Zhu Y

Aims

Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis.

Methods

The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene.


Bone & Joint Research
Vol. 12, Issue 8 | Pages 467 - 475
2 Aug 2023
Wu H Sun D Wang S Jia C Shen J Wang X Hou C Xie Z Luo F

Aims

This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis.

Methods

We included adult patients with limb osteomyelitis who received debridement and ALCS insertion into the bone defect as definitive management between 2013 and 2020 in our clinical centre. The follow-up time was at least two years. Data on patients’ demographics, clinical characteristics, and infection recurrence were retrospectively collected and analyzed.


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 6 | Pages 375 - 386
12 Jun 2023
Li Z

Aims

Long non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP.

Methods

Using quantitative real-time polymerase chain reaction (qRT-PCR), osteogenesis-related genes (alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2)), PCBP1-AS1, microRNA (miR)-126-5p, group I Pak family member p21-activated kinase 2 (PAK2), and their relative expression levels were determined. Western blotting was used to examine the expression of PAK2 protein. Cell Counting Kit-8 (CCK-8) assay was used to measure cell proliferation. To examine the osteogenic differentiation, Alizarin red along with ALP staining was used. RNA immunoprecipitation assay and bioinformatics analysis, as well as a dual-luciferase reporter, were used to study the association between PCBP1-AS1, PAK2, and miR-126-5p.


Bone & Joint Research
Vol. 12, Issue 4 | Pages 274 - 284
11 Apr 2023
Du X Jiang Z Fang G Liu R Wen X Wu Y Hu S Zhang Z

Aims

This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA).

Methods

Meniscus and synovial tissue were collected from 14 patients with and without OA. MCL and FLS proteins were extracted and analyzed by liquid chromatography‒mass spectrometry (LC‒MS). The roles of MCL and adenine nucleotide translocase 3 (ANT3) in FLSs were examined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, and transmission electron microscopy. Histological analysis was performed to determine ANT3 expression levels in a male mouse model.


Bone & Joint Research
Vol. 12, Issue 4 | Pages 245 - 255
3 Apr 2023
Ryu S So J Ha Y Kuh S Chin D Kim K Cho Y Kim K

Aims

To determine the major risk factors for unplanned reoperations (UROs) following corrective surgery for adult spinal deformity (ASD) and their interactions, using machine learning-based prediction algorithms and game theory.

Methods

Patients who underwent surgery for ASD, with a minimum of two-year follow-up, were retrospectively reviewed. In total, 210 patients were included and randomly allocated into training (70% of the sample size) and test (the remaining 30%) sets to develop the machine learning algorithm. Risk factors were included in the analysis, along with clinical characteristics and parameters acquired through diagnostic radiology.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 212 - 218
9 Mar 2023
Buchalter DB Kirby DJ Anil U Konda SR Leucht P

Aims

Glucose-insulin-potassium (GIK) is protective following cardiac myocyte ischaemia-reperfusion (IR) injury, however the role of GIK in protecting skeletal muscle from IR injury has not been evaluated. Given the similar mechanisms by which cardiac and skeletal muscle sustain an IR injury, we hypothesized that GIK would similarly protect skeletal muscle viability.

Methods

A total of 20 C57BL/6 male mice (10 control, 10 GIK) sustained a hindlimb IR injury using a 2.5-hour rubber band tourniquet. Immediately prior to tourniquet placement, a subcutaneous osmotic pump was placed which infused control mice with saline (0.9% sodium chloride) and treated mice with GIK (40% glucose, 50 U/l insulin, 80 mEq/L KCl, pH 4.5) at a rate of 16 µl/hr for 26.5 hours. At 24 hours following tourniquet removal, bilateral (tourniqueted and non-tourniqueted) gastrocnemius muscles were triphenyltetrazolium chloride (TTC)-stained to quantify percentage muscle viability. Bilateral peroneal muscles were used for gene expression analysis, serum creatinine and creatine kinase activity were measured, and a validated murine ethogram was used to quantify pain before euthanasia.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 155 - 164
1 Mar 2023
McCarty CP Nazif MA Sangiorgio SN Ebramzadeh E Park S

Aims

Taper corrosion has been widely reported to be problematic for modular total hip arthroplasty implants. A simple and systematic method to evaluate taper damage with sufficient resolution is needed. We introduce a semiquantitative grading system for modular femoral tapers to characterize taper corrosion damage.

Methods

After examining a unique collection of retrieved cobalt-chromium (CoCr) taper sleeves (n = 465) using the widely-used Goldberg system, we developed an expanded six-point visual grading system intended to characterize the severity, visible material loss, and absence of direct component contact due to corrosion. Female taper sleeve damage was evaluated by three blinded observers using the Goldberg scoring system and the expanded system. A subset (n = 85) was then re-evaluated following destructive cleaning, using both scoring systems. Material loss for this subset was quantified using metrology and correlated with both scoring systems.


Bone & Joint Research
Vol. 11, Issue 12 | Pages 873 - 880
1 Dec 2022
Watanabe N Miyatake K Takada R Ogawa T Amano Y Jinno T Koga H Yoshii T Okawa A

Aims

Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery’s outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis.

Methods

This single-centre retrospective study included 398 hip joints of patients who underwent THA. Using medical records, we examined preoperative bone mineral density measures of the hip and lumbar spine using dual energy X-ray absorptiometry (DXA) scans and the medications used to treat osteoporosis at the time of admission. We also assessed the following osteoporosis-related biomarkers: tartrate-resistant acid phosphatase 5b (TRACP-5b); total procollagen type 1 amino-terminal propeptide (total P1NP); intact parathyroid hormone; and homocysteine.


Bone & Joint Research
Vol. 11, Issue 12 | Pages 862 - 872
1 Dec 2022
Wang M Tan G Jiang H Liu A Wu R Li J Sun Z Lv Z Sun W Shi D

Aims

Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA.

Methods

We used four groups of transcription profiles acquired from the Gene Expression Omnibus database, including articular cartilage, meniscus, synovium, and subchondral bone, to screen differentially expressed genes during OA. Potential crosstalk between tissues was depicted by ligand-receptor pairs.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 518 - 527
17 Aug 2022
Hu W Lin J Wei J Yang Y Fu K Zhu T Zhu H Zheng X

Aims

To evaluate inducing osteoarthritis (OA) by surgical destabilization of the medial meniscus (DMM) in mice with and without a stereomicroscope.

Methods

Based on sample size calculation, 70 male C57BL/6 mice were randomly assigned to three surgery groups: DMM aided by a stereomicroscope; DMM by naked eye; or sham surgery. The group information was blinded to researchers. Mice underwent static weightbearing, von Frey test, and gait analysis at two-week intervals from eight to 16 weeks after surgery. Histological grade of OA was determined with the Osteoarthritis Research Society International (OARSI) scoring system.


Aims

To identify the responsiveness, minimal clinically important difference (MCID), minimal clinical important change (MIC), and patient-acceptable symptom state (PASS) thresholds in the 36-item Short Form Health Survey questionnaire (SF-36) (v2) for each of the eight dimensions and the total score following total knee arthroplasty (TKA).

Methods

There were 3,321 patients undergoing primary TKA with preoperative and one-year postoperative SF-36 scores. At one-year patients were asked how satisfied they were and “How much did the knee arthroplasty surgery improve the quality of your life?”, which was graded as: great, moderate, little (n = 277), none (n = 98), or worse.


Aims

Treatment outcomes for methicillin-resistant Staphylococcus aureus (MRSA) periprosthetic joint infection (PJI) using systemic vancomycin and antibacterial cement spacers during two-stage revision arthroplasty remain unsatisfactory. This study explored the efficacy and safety of intra-articular vancomycin injections for PJI control after debridement and cement spacer implantation in a rat model.

Methods

Total knee arthroplasty (TKA), MRSA inoculation, debridement, and vancomycin-spacer implantation were performed successively in rats to mimic first-stage PJI during the two-stage revision arthroplasty procedure. Vancomycin was administered intraperitoneally or intra-articularly for two weeks to control the infection after debridement and spacer implantation.


Bone & Joint Research
Vol. 11, Issue 4 | Pages 239 - 250
20 Apr 2022
Stewart CC O’Hara NN Bzovsky S Bahney CS Sprague S Slobogean GP

Aims

Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture.

Methods

A total of 102 participants aged 18 to 50 years (median 28 years (interquartile range 23 to 35)), receiving an intramedullary nail for a tibial or femoral shaft fracture, were enrolled in a randomized controlled trial comparing vitamin D3 supplementation to placebo. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and N-terminal propeptide of type I procollagen (P1NP; bone formation marker) were measured at baseline, six weeks, and 12 weeks post-injury. Clinical and radiological fracture healing was assessed at three months.


Bone & Joint Research
Vol. 11, Issue 2 | Pages 91 - 101
1 Feb 2022
Munford MJ Stoddart JC Liddle AD Cobb JP Jeffers JRT

Aims

Unicompartmental and total knee arthroplasty (UKA and TKA) are successful treatments for osteoarthritis, but the solid metal implants disrupt the natural distribution of stress and strain which can lead to bone loss over time. This generates problems if the implant needs to be revised. This study investigates whether titanium lattice UKA and TKA implants can maintain natural load transfer in the proximal tibia.

Methods

In a cadaveric model, UKA and TKA procedures were performed on eight fresh-frozen knee specimens, using conventional (solid) and titanium lattice tibial implants. Stress at the bone-implant interfaces were measured and compared to the native knee.


Bone & Joint Research
Vol. 10, Issue 12 | Pages 830 - 839
15 Dec 2021
Robertson G Wallace R Simpson AHRW Dawson SP

Aims

Assessment of bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA) is a well-established clinical technique, but it is not available in the acute trauma setting. Thus, it cannot provide a preoperative estimation of BMD to help guide the technique of fracture fixation. Alternative methods that have been suggested for assessing BMD include: 1) cortical measures, such as cortical ratios and combined cortical scores; and 2) aluminium grading systems from preoperative digital radiographs. However, limited research has been performed in this area to validate the different methods. The aim of this study was to investigate the evaluation of BMD from digital radiographs by comparing various methods against DXA scanning.

Methods

A total of 54 patients with distal radial fractures were included in the study. Each underwent posteroanterior (PA) and lateral radiographs of the injured wrist with an aluminium step wedge. Overall 27 patients underwent routine DXA scanning of the hip and lumbar spine, with 13 undergoing additional DXA scanning of the uninjured forearm. Analysis of radiographs was performed on ImageJ and Matlab with calculations of cortical measures, cortical indices, combined cortical scores, and aluminium equivalent grading.


Bone & Joint Research
Vol. 10, Issue 11 | Pages 723 - 733
1 Nov 2021
Garner AJ Dandridge OW Amis AA Cobb JP van Arkel RJ

Aims

Bi-unicondylar arthroplasty (Bi-UKA) is a bone and anterior cruciate ligament (ACL)-preserving alternative to total knee arthroplasty (TKA) when the patellofemoral joint is preserved. The aim of this study is to investigate the clinical outcomes and biomechanics of Bi-UKA.

Methods

Bi-UKA subjects (n = 22) were measured on an instrumented treadmill, using standard gait metrics, at top walking speeds. Age-, sex-, and BMI-matched healthy (n = 24) and primary TKA (n = 22) subjects formed control groups. TKA subjects with preoperative patellofemoral or tricompartmental arthritis or ACL dysfunction were excluded. The Oxford Knee Score (OKS) and EuroQol five-dimension questionnaire (EQ-5D) were compared. Bi-UKA, then TKA, were performed on eight fresh frozen cadaveric knees, to investigate knee extensor efficiency under controlled laboratory conditions, using a repeated measures study design.


Bone & Joint Research
Vol. 10, Issue 10 | Pages 693 - 703
1 Oct 2021
Wang X Wang D Xia P Cheng K Wang Q Wang X Lin Q Song J Chen A Li X

Aims

To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMDSV) for alleviation of the progression of osteoarthritis (OA) in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ).

Methods

In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMDSV on alternate days for four weeks. Chondrocytes were also treated with PPARγ inhibitor, PPARγ inhibitor+ UTMDSV, and UTMDSV. The cholesterol efflux rate and triglyceride levels were measured using an assay kit and oil red O staining, respectively. In vivo, the OA rabbits were treated with a single intra-articular injection of UTMD, SV, and UTMDSV every seven days for four weeks. Cartilage histopathology was assessed by safranin-O staining and the Mankin score. Total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) in rabbit knee synovial fluid were detected by enzyme-marker assay. Aggrecan, collagen II, and PPARγ expression levels were analyzed by Western blotting (WB).


Bone & Joint Research
Vol. 10, Issue 10 | Pages 677 - 689
1 Oct 2021
Tamaddon M Blunn G Xu W Alemán Domínguez ME Monzón M Donaldson J Skinner J Arnett TR Wang L Liu C

Aims

Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone.

Methods

The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety.