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Bone & Joint Research
Vol. 12, Issue 11 | Pages 691 - 701
3 Nov 2023
Dai Z Chen Y He E Wang H Guo W Wu Z Huang K Zhao Q

Aims

Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis.

Methods

Blood and femoral bone marrow suspension IL-19 levels were first measured in the lipopolysaccharide (LPS)-induced bone loss model. Small interfering RNA (siRNA) was applied to knock down IL-19 for further validation. Thereafter, osteoclast production was stimulated with IL-19 in combination with mouse macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The effect of IL-19 was subsequently evaluated using tartrate-resistant acid phosphatase (TRAP) staining and quantitative real-time polymerase chain reaction (RT-qPCR). The effect of IL-19 on osteoprotegerin (OPG) was then assessed using in vitro recombinant IL-19 treatment of primary osteoblasts and MLO-Y4 osteoblast cell line. Finally, transient transfection experiments and chromatin immunoprecipitation (ChIP) experiments were used to examine the exact mechanism of action.


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 551 - 558
1 May 2023
Wang H Ji T Qu H Yan T Li D Yang R Tang X Guo W

Aims

The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours.

Methods

ICG fluorescence imaging was performed during surgery in 34 patients with bone and soft-tissue tumours. ICG was administered intravenously at a dose of 2 mg/kg over a period of 60 minutes on the day prior to surgery. The tumour stain rate and signal-to-background ratio of each tumour were post hoc analyzed. After tumour resection, the tumour bed was scanned to locate sites with fluorescence residuals, which were subsequently inspected and biopsied.


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 48 - 48
4 Apr 2023
Yang Y Li Y Pan Q Wang H Bai S Pan X Ling K Li G
Full Access

Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remain a challenge. A novel surgical technique named Tibial Cortex Transverse Transport has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In present study, we aimed to explore the wound healing effects after undergoing this novel technique via multiple ways.

A novel rat model of Tibial Cortex Transverse Transport was established with a designed external fixator and effects on wound healing were investigated. All rats were randomized into 3 groups, with 12 rats per group: sham group (negative control), fixator group (positive control) and Tibial Cortex Transverse Transport group. Laser speckle perfusion imaging, vessel perfusion, histology and immunohistochemistry were used to evaluate the wound healing processes.

Gross and histological examinations showed that Tibial Cortex Transverse Transport technique accelerated wound closure and enhanced the quality of the newly formed skin tissues. In Tibial Cortex Transverse Transport group, HE staining demonstrated a better epidermis and dermis recovery, while immune-histochemical staining showed that Tibial Cortex Transverse Transport technique promoted local collagen deposition. Tibial Cortex Transverse Transport technique also benefited to angiogenesis and immunomodulation. In Tibial Cortex Transverse Transport group, blood flow in the wound area was higher than that ofother groups according to laser speckle imaging with more blood vessels observed. Enhanced neovascularization was seen in the Tibial Cortex Transverse Transport group with double immune-labelling of CD31 and α-SMA. The M2 macrophages at the wound site in the Tibial Cortex Transverse Transport group was also increased.

Tibial cortex transverse transport technique accelerated wound healing through enhanced angiogenesis and immunomodulation.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 453 - 464
20 Jul 2022
Wang H Shi Y He F Ye T Yu S Miao H Liu Q Zhang M

Aims

Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). Growth differentiation factor 11 (GDF11) is crucial in inhibiting the differentiation of bone marrow mesenchymal stem cells into adipocytes. However, whether GDF11 participates in the abnormal adipogenesis of chondrocytes in OA cartilage is still unclear.

Methods

Six-week-old female mice were subjected to unilateral anterior crossbite (UAC) to induce OA in the temporomandibular joint (TMJ). Histochemical staining, immunohistochemical staining (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. Primary condylar chondrocytes of rats were stimulated with fluid flow shear stress (FFSS) and collected for oil red staining, immunofluorescence staining, qRT-PCR, and immunoprecipitation analysis.


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 189 - 199
13 Apr 2022
Yang Y Li Y Pan Q Bai S Wang H Pan X Ling K Li G

Aims

Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model.

Methods

A novel rat model of TTT was established with a designed external fixator, and effects on wound healing were investigated. Laser speckle perfusion imaging, vessel perfusion, histology, and immunohistochemistry were used to evaluate the wound healing processes.


The Bone & Joint Journal
Vol. 104-B, Issue 2 | Pages 193 - 199
1 Feb 2022
Wang Q Wang H A G Xiao T Kang P

Aims

This study aimed to use intraoperative free electromyography to examine how the placement of a retractor at different positions along the anterior acetabular wall may affect the femoral nerve during total hip arthroplasty (THA) when undertaken using the direct anterior approach (THA-DAA).

Methods

Intraoperative free electromyography was performed during primary THA-DAA in 82 patients (94 hips). The highest position of the anterior acetabular wall was defined as the “12 o’clock” position (middle position) when the patient was in supine position. After exposure of the acetabulum, a retractor was sequentially placed at the ten, 11, 12, one, and two o’clock positions (right hip; from superior to inferior positions). Action potentials in the femoral nerve were monitored with each placement, and the incidence of positive reactions (defined as explosive, frequent, or continuous action potentials, indicating that the nerve was being compressed) were recorded as the primary outcome. Secondary outcomes included the incidence of positive reactions caused by removing the femoral head, and by placing a retractor during femoral exposure; and the incidence of femoral nerve palsy, as detected using manual testing of the strength of the quadriceps muscle.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 411 - 424
14 Jul 2021
Zhao D Ren B Wang H Zhang X Yu M Cheng L Sang Y Cao S Thieringer FM Zhang D Wan Y Liu C

Aims

The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration.

Methods

IL4 at concentrations of 0, 30, and 100 ng/ml was used at day 3 to create a biomimetic environment for bone marrow mesenchymal stromal cell (BMMSC) osteogenesis and macrophage polarization on the DT. The osteogenic and immune responses of BMMSCs and macrophages were evaluated respectively.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 401 - 410
13 Jul 2021
Liu Z Wang H Wang S Gao J Niu L

Aims

Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model.

Methods

The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA).


The Bone & Joint Journal
Vol. 103-B, Issue 2 | Pages 382 - 390
1 Feb 2021
Wang H Tang X Ji T Yan T Yang R Guo W

Aims

There is an increased risk of dislocation of the hip after the resection of a periacetabular tumour and endoprosthetic reconstruction of the defect in the hemipelvis. The aim of this study was to determine the rate and timing of dislocation and to identify its risk factors.

Methods

To determine the dislocation rate, we conducted a retrospective single-institution study of 441 patients with a periacetabular tumour who had undergone a standard modular hemipelvic endoprosthetic reconstruction between 2003 and 2019. After excluding ineligible patients, 420 patients were enrolled. Patient-specific, resection-specific, and reconstruction-specific variables were studied using univariate and multivariate analyses.


The Bone & Joint Journal
Vol. 102-B, Issue 8 | Pages 981 - 996
1 Aug 2020
Yang Y Zhao H Chai Y Zhao D Duan L Wang H Zhu J Yang S Li C Chen S Chae S Song J Wang X Yu X

Aims

Whether to perform hybrid surgery (HS) in contrast to anterior cervical discectomy and fusion (ACDF) when treating patients with multilevel cervical disc degeneration remains a controversial subject. To resolve this we have undertaken a meta-analysis comparing the outcomes from HS with ACDF in this condition.

Methods

Seven databases were searched for studies of HS and ACDF from inception of the study to 1 September 2019. Both random-effects and fixed-effects models were used to evaluate the overall effect of the C2-C7 range of motion (ROM), ROM of superior/inferior adjacent levels, adjacent segment degeneration (ASD), heterotopic ossification (HO), complications, neck disability index (NDI) score, visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, Odom’s criteria, blood loss, and operating and hospitalization time. To obtain more credible results contour-enhanced funnel plots, Egger’s and Begg’s tests, meta-regression, and sensitivity analyses were performed.


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1209 - 1217
1 Oct 2019
Zeng C Lane NE Englund M Xie D Chen H Zhang Y Wang H Lei G

Aims

There is an increasing demand for hip arthroplasty in China. We aimed to describe trends in in-hospital mortality after this procedure in China and to examine the potential risk factors.

Patients and Methods

We included 210 450 patients undergoing primary hip arthroplasty registered in the Hospital Quality Monitoring System in China between 2013 and 2016. In-hospital mortality after hip arthroplasty and its relation to potential risk factors were assessed using multivariable Poisson regression.


The Bone & Joint Journal
Vol. 100-B, Issue 8 | Pages 1025 - 1032
1 Aug 2018
Wang D Wang H Luo Z Meng W Pei F Li Q Zhou Z Zeng W

Aims

The aim of this study was to identify the most effective regimen of multiple doses of oral tranexamic acid (TXA) in achieving maximum reduction of blood loss in total knee arthroplasty (TKA).

Patients and Methods

In this randomized controlled trial, 200 patients were randomized to receive a single dose of 2.0 g of TXA orally two hours preoperatively (group A), a single dose of TXA followed by 1.0 g orally three hours postoperatively (group B), a single dose of TXA followed by 1.0 g three and nine hours postoperatively (group C), or a single dose of TXA followed by 1.0 g orally three, nine, and 15 hours postoperatively (group D). All patients followed a routine enhanced-recovery protocol. The primary outcome measure was the total blood loss. Secondary outcome measures were hidden blood loss (HBL), reduction in the level of haemoglobin, the rate of transfusion and adverse events.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_20 | Pages 20 - 20
1 Dec 2017
Xu L Chen X Wang H Wang F Wang Q
Full Access

Over the past decades, computer-aided navigation system has experienced tremendous development for minimising the risks and improving the precision of the surgery. Nowadays, some commercially-available and self-developed surgical navigation systems have already been tested and proved successfully for clinical applications. However, all of these systems use computer screen to render the navigation information such as the real-time position and orientation of the surgical instrument, virtual path of preoperative surgical planning, so that the surgeons have to switch between the actual operation site and computer screen which is inconvenient and impact the continuity of surgery. In recent years, Augmented Reality (AR)- based surgical navigation is a promising technology for clinical applications. In the AR system, virtual and actual reality are mixed, offering real-time, high-quality visualisation of an extensive variety of information to the users.

Therefore, in this study, a pilot study of a surgical navigation system for orthopaedics based on optical see-through augmented reality (AR-SNS) is presented, which encompasses the preoperative surgical planning, calibration, registration, and intra-operative tracking. With the aid of AR-SNS, the surgeon wearing the optical see-through head-mounted display can obtain a fused image that the 3D virtual critical anatomical structures are aligned with the actual structures of patient in intra-operative real-world scenario, so that some disadvantages of the traditional surgical navigation are overcome (For example, surgeon is no longer obliged to switch between the real operation scenario and computer screen), and the safety, accuracy, and reliability of the surgery may be improved.


Objectives

The lack of effective treatment for cartilage defects has prompted investigations using tissue engineering techniques for their regeneration and repair. The success of tissue-engineered repair of cartilage may depend on the rapid and efficient adhesion of transplanted cells to a scaffold. Our aim in this study was to repair full-thickness defects in articular cartilage in the weight-bearing area of a porcine model, and to investigate whether the CD44 monoclonal antibody biotin-avidin (CBA) binding technique could provide satisfactory tissue-engineered cartilage.

Methods

Cartilage defects were created in the load-bearing region of the lateral femoral condyle of mini-type pigs. The defects were repaired with traditional tissue-engineered cartilage, tissue-engineered cartilage constructed with the biotin-avidin (BA) technique, tissue-engineered cartilage constructed with the CBA technique and with autologous cartilage. The biomechanical properties, Western blot assay, histological findings and immunohistochemical staining were explored.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_6 | Pages 77 - 77
1 Mar 2017
Wang H Foster J Franksen N Rolston L
Full Access

Background

More and more patients with end-stage knee OA are treated with total knee replacements (TKR). A modern TKR (Persona PS system, Zimmer Inc.) was designed with the hope to improve fit by providing additional sizing options on the femur and tibia. To date, there is very little information regarding the knee strength and knee mechanics during gait after the TKR. Furthermore, as a great percentage of knee OA patients have OA limited in one knee compartment and in the patellofemoral joint, a bi-compartmental knee replacement (BKR) (iDUO system, ConforMIS Inc.) was designed to treat OA at these affected areas. The BKR re-creates the individual's knee shape while correcting for any deformity. In addition, the BKR procedure results in less bone loss and retains the cruciate ligaments. To date, the influence of the BKR on knee strength and knee mechanics remains unknown. The purpose of the study was to evaluate knee strength and mechanics during level walking after the TKR and BKR surgeries.

Methods

Twelve healthy control participants (age=57±6 yr.; mass=82±11 kg; height=175±11 cm), eight patients (age=63±10 yr.; mass=87±20 kg; height=166±8 cm) with ten BKR systems (post-op time = 17±9 mo.), and nine patients (age=65±9 yr.; mass=90±35 kg; Height=169±12 cm) with twelve TKR systems (post-op time = 14±5 mo.) participated in the study. In a laboratory setting, maximal isometric knee strength was evaluated. Motion capture and 3D kinematic and kinetic analyses were conducted for level walking. One way ANOVA was used to determine differences among the BKR, TKR, and the healthy control knees.


Bone & Joint Research
Vol. 5, Issue 9 | Pages 412 - 418
1 Sep 2016
Ye S Ju B Wang H Lee K

Objectives

Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration.

Methods

Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_10 | Pages 27 - 27
1 May 2016
Sheng P Li Z Luo G Wang H Chen W Zhang Y Yang X
Full Access

Objective

To investigate the biomechanical mechanism and report preliminary clinical efficacy of eccentric rotational acetabular osteotomy (ERAO) when conduct treatment for developmental dysplasia of the hip (DDH).

Methods

Biomechanical model of the hip joint was established on six female cadaveric hips embalmed by formalin and stimulate ERAO was then performed on the model. Vertical force was loaded on the cadaveric spine from 0 N to 500 N and strain value on femoral head was measured preoperatively and postoperatively when loading force on spine reached the point of 100, 200, 300, 400 and 500 N. Stress value were then calculated base on the measurements. Besides, we reported postoperative follow up cases which were underwent ERAO to treat DDH in our hospital from July 2007 to October 2014. A total of 25 patients (26 hips) were reported, including 6 males and 19 females. Age varies from 11 to 57 years old, and the average age was 31 years old. Postoperative hip function was evaluated by Harris hip score and anteroposterior X⁃ray of pelvic was taken preoperatively and postoperatively to measure the Acetabular⁃head index (AHI), CE angle and Sharp angle.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_4 | Pages 4 - 4
1 Jan 2016
Yang X Chen W Yu S Zhang Y Luo G Wang H Sheng P
Full Access

Objective

To investigate the biomechanical basis and report preliminary clinical efficacy of eccentric rotational acetabular osteotomy (ERAO) when treating developmental dysplasia of the hip (DDH).

Methods

Biomechanical model of the hip joint was established on cadaveric hips. After performed ERAO on the biomechanical model, we explored the impact of this surgery on biomechanics of the hip joint. Meanwhile, we reported postoperative follow-up cases who underwent ERAO in our hospital between November 2007 to July 2012. A total of 14 patients (15 hips) were reported, including 4 males and 10 females, mean age was 30 years old. Harris hip score was defined as clinical evaluation standard and radiographic assessment was based on the measurement and further comparison of pre- and post-operative AHI (Acetabular-head index), CE angle (Center-edge angle) and Sharp angle.