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Bone & Joint Research
Vol. 14, Issue 3 | Pages 209 - 222
10 Mar 2025
Xiao Y Yue Z Zijing H Yao Z Sui M Xuemin Z Qiang Z Xiao Y Dapeng R

Aims. Excessive chondrocyte hypertrophy is a common feature in cartilage degeneration which is susceptible to joint overloading, but the relationship between mechanical overloading and chondrocyte hypertrophy still remains elusive. The aim of our study was to explore the mechanism of mechanical compression-induced chondrocyte hypertrophy. Methods. In this study, the temporomandibular joint (TMJ) degeneration model was built through forced mandibular retrusion (FMR)-induced compression in TMJ. Chondrocytes were also mechanically compressed in vitro. The role of O-GlcNAcylation in mechanical compression-induced chondrocyte hypertrophy manifested through specific activator Thiamet G and inhibitor OSMI-1. Results. Both in vivo and in vitro data revealed that chondrocyte hypertrophic differentiation is promoted by compression. Immunofluorescent and immunoblotting results showed that protein pan-O-GlcNAcylation levels were elevated in these hypertrophic chondrocytes. Pharmacologically inhibiting protein pan-O-GlcNAcylation by OSMI-1 partially mitigated the compression-induced hypertrophic differentiation of chondrocytes. Specifically, runt-related transcription factor 2 (Runx2) and SRY-Box 9 transcription factor (Sox9) were subjected to modification of O-GlcNAcylation under mechanical compression, and pharmacological activation or inhibition of O-GlcNAcylation affected the transcriptional activity of Runx2 but not Sox9. Furthermore, compression-induced protein pan-O-GlcNAcylation in chondrocytes was induced by enhanced expression of glucose transporter 1 (GLUT1), and depletion of GLUT1 by WZB117 dampened the effect of compression on chondrocyte hypertrophy. Conclusion. Our study proposes a novel function of GLUT1-mediated protein O-GlcNAcylation in driving compression-induced hypertrophic differentiation of chondrocytes by O-GlcNAc modification of Runx2, which promoted its transcriptional activity and strengthened the expressions of downstream hypertrophic marker. Cite this article: Bone Joint Res 2025;14(3):209–222


Bone & Joint Research
Vol. 13, Issue 12 | Pages 703 - 715
3 Dec 2024
Raza IGA Snelling SJB Mimpen JY

Aims

Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease.

Methods

A systematic search strategy, devised using relevant matrix, tissue, and disease nomenclature, was run through the MEDLINE, Embase, and Scopus databases. Demographic, clinical, and biological data were extracted from eligible studies. Bias analysis was performed.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 124 - 124
11 Apr 2023
Woodford S Robinson D Lee P Abduo J Dimitroulis G Ackland D
Full Access

Total temporomandibular joint (TMJ) replacements reduce pain and improve quality of life in patients suffering from end-stage TMJ disorders, such as osteoarthritis and trauma. Jaw kinematics measurements following TMJ arthroplasty provide a basis for evaluating implant performance and jaw function. The aim of this study is to provide the first measurements of three-dimensional kinematics of the jaw in patients following unilateral and bilateral prosthetic TMJ surgeries. Jaw motion tracking experiments were performed on 7 healthy control participants, 3 unilateral and 1 bilateral TMJ replacement patients. Custom-made mouthpieces were manufactured for each participant's mandibular and maxillary teeth, with each supporting three retroreflective markers anterior to the participant's lip line. Participants performed 15 trials each of maximum jaw opening, lateral and protrusive movements. Marker trajectories were simultaneously measured using an optoelectronic tracking system. Laser scans taken of each dental plate, together with CT scans of each patient, were used to register the plate position to each participant's jaw geometry, allowing 3D condylar motion to be quantified from the marker trajectories. The maximum mouth opening capacity of joint replacement patients was comparable to healthy controls with average incisal inferior translations of 37.5mm, 38.4mm and 33.6mm for the controls, unilateral and bilateral joint replacement patients respectively. During mouth opening the maximum anterior translation of prosthetic condyles was 2.4mm, compared to 10.6mm for controls. Prosthetic condyles had limited anterior motion compared to natural condyles, in unilateral patients this resulted in asymmetric opening and protrusive movements and the capacity to laterally move their jaw towards their pathological side only. For the bilateral patient, protrusive and lateral jaw movement capacity was minimal. Total TMJ replacement surgery facilitates normal mouth opening capacity and lateral and inferior condylar movements but limits anterior condylar motion. This study provides future direction for TMJ implant design


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. Results. Abnormal adipogenesis, characterized by increased expression of CCAAT/enhancer-binding protein α (CEBPα), fatty acid binding protein 4 (FABP4), Perilipin1, Adiponectin (AdipoQ), and peroxisome proliferator-activated receptor γ (PPARγ), was enhanced in the degenerative cartilage of TMJ OA in UAC mice, accompanied by decreased expression of GDF11. After FFSS stimulation, there were fat droplets in the cytoplasm of cultured cells with increased expression of PPARγ, CEBPα, FABP4, Perilipin1, and AdipoQ and decreased expression of GDF11. Exogenous GDF11 inhibited increased lipid droplets and expression of AdipoQ, CEBPα, and FABP4 induced by FFSS stimulation. GDF11 did not affect the change in PPARγ expression under FFSS, but promoted its post-translational modification by small ubiquitin-related modifier (SUMOylation). Local injection of GDF11 alleviated TMJ OA-related cartilage degeneration and abnormal adipogenesis in UAC mice. Conclusion. Abnormal adipogenesis of chondrocytes and decreased GDF11 expression were observed in degenerative cartilage of TMJ OA. GDF11 supplementation effectively inhibits the adipogenesis of chondrocytes and thus alleviates TMJ condylar cartilage degeneration. GDF11 may inhibit the abnormal adipogenesis of chondrocytes by affecting the SUMOylation of PPARγ. Cite this article: Bone Joint Res 2022;11(7):453–464


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. Results. Interleukin (IL)-1β inhibited the chondrogenic differentiation potential of SMSCs, while the HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and panobinostat (LBH589), attenuated inhibition of IL-1β-induced SMSC chondrogenesis. Additionally, SAHA attenuated the destruction of condylar cartilage in rat TMJ arthritis model. IL-6 (p < 0.001) and matrix metalloproteinase 13 (MMP13) (p = 0.006) were significantly upregulated after IL-1β stimulation, while SAHA and LBH589 attenuated IL-6 and MMP13 expression, which was upregulated by IL-1β in vitro. Silencing of IL-6 significantly downregulated MMP13 expression and attenuated IL-1β-induced chondrogenesis inhibition of SMSCs. Conclusion. HDAC inhibitors SAHA and LBH589 attenuated chondrogenesis inhibition of SMSC induced by IL-1β in TMJ, and inhibition of IL-6/MMP13 pathway activation contributes to this biological progress. This study provides a theoretical basis for the application of HDAC inhibitors in the treatment of TMJ arthritis. Cite this article: Bone Joint Res 2022;11(1):40–48


Bone & Joint Research
Vol. 10, Issue 7 | Pages 437 - 444
27 Jul 2021
Yan F Feng J Yang L Shi C

Aims

The aim of our study is to investigate the effect induced by alternated mechanical loading on Notch-1 in mandibular condylar cartilage (MCC) of growing rabbits.

Methods

A total of 64 ten-day-old rabbits were randomly divided into two groups according to dietary hardness: normal diet group (pellet) and soft diet group (powder). In each group, the rabbits were further divided into four subgroups by feeding time: two weeks, four weeks, six weeks, and eight weeks. Animals would be injected 5-bromo-2′-deoxyuridine (BrdU) every day for one week before sacrificing. Histomorphometric analysis of MCC thickness was performed through haematoxylin and eosin (HE) staining. Immunochemical analysis was done to test BrdU and Notch-1. The quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to measure expression of Notch-1, Jagged-1, and Delta-like 1 (Dll-1).


Bone & Joint Research
Vol. 9, Issue 10 | Pages 689 - 700
7 Oct 2020
Zhang A Ma S Yuan L Wu S Liu S Wei X Chen L Ma C Zhao H

Aims

The study aimed to determine whether the microRNA miR21-5p (MiR21) mediates temporomandibular joint osteoarthritis (TMJ-OA) by targeting growth differentiation factor 5 (Gdf5).

Methods

TMJ-OA was induced in MiR21 knockout (KO) mice and wild-type (WT) mice by a unilateral anterior crossbite (UAC) procedure. Mouse tissues exhibited histopathological changes, as assessed by: Safranin O, toluidine blue, and immunohistochemistry staining; western blotting (WB); and quantitative real-time polymerase chain reaction (RT-qPCR). Mouse condylar chondrocytes were transfected with a series of MiR21 mimic, MiR21 inhibitor, Gdf5 siRNA (si-GDF5), and flag-GDF5 constructs. The effects of MiR-21 and Gdf5 on the expression of OA related molecules were evaluated by immunofluorescence, alcian blue staining, WB, and RT-qPCR.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_2 | Pages 51 - 51
1 Jan 2017
Ramos A Mesnard M
Full Access

The Temporomandibular joint (TMJ) is a complex and important joint for daily activities, and the alloplastic implant is recommended as the best solution, after repeated surgeries, failed autogenous grafts, highly inflammatory metabolic arthritis, fibrous or bony ankyloses. Some complications in total TMJ replacement are associated with implant design, screw fixation failure, implant displacement, fibrous tissue formation, (Speculand, et al. 2000). Some numeric studies evaluate the number of screws needed to guarantee the good fixation and suggest a minimum of three (Ramos et al. 2015), but is a controversy conclusion. The Biomet Microfixation TMJ stock prosthesis, Jacksonville, FL, USA is one of the three or four in the market. Clinical studies published by this device between 2005 and 2015 indicate a success rate of around 84 to 91% with improvements in mouth opening, a decrease in pain score and improved quality of life. The present study analyses experimentally the load transfer of this device. The intact, clean cadaveric ramus was instrumented with four rosettes model (KFG-1-120-D17-11 L3M2S, by Kywoa Electronic Instruments Co™, Japan), one in lateral region, two in lateral region and one in lingual face. The condyle was loaded with the temporal reaction; the load was applied constant velocity of 1mm/min in three continuum phases and with three stops at 100N, 200N and 300N. Next, the Biomet microfixation implant was fixed to the same cadaveric mandibular ramus after resection. The implant was 50mm in length. It was fixed with five 6AL/4V Titanium self-tapping screws with 2.7mm diameter were long enough to establish a bi-cortical support. The screws were screwed into the bone with a torque-screwdriver a constant torque of 0.2Nm. The same rosettes were analyzed before and after implantation and the mandible displacement two. The experimental results for the mandibular ramus present a linear behavior up to 300N load in condyle, with the Biomet implant influencing strain distribution; the maximum influence was near the implant (rosette #4) is around 59%. The average vertical displacement of the mandibular ramus (300N) was measured by machine: 1.18 (±0.02) mm for the intact mandibular ramus and 1.21 (±0.02) mm for the implanted one, which represents a 2.8% differences between the experimental models and reduce of stiffness. The maximum principal strain deformation was observed in the rosette #3 with 1360µε more 20% than the intact mandible for 300N of reaction. The experimental results show that the Biomet TMJ mandibular ramus implant changes the load transfer in the ramus, compared to the intact, with its strain shielding effect. The results indicate the minimum number of screws is three to guarantee a good load transfer but the surface preparation of condyle presents an important factor


Bone & Joint 360
Vol. 4, Issue 5 | Pages 16 - 18
1 Oct 2015

The October 2015 Wrist & Hand Roundup360 looks at: Base of thumb arthritis – steroids not a waste of time; De Quervain’s tenosynovitis and steroids; Use your therapy time wisely!; Excision osteotomy for the carpometacarpal joint?; CORDLESS at five years?; Arthroscopy again of no benefit?; Distal radius stirring up trouble again!; Scaphoid arthroscopy under the spotlight


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_9 | Pages 7 - 7
1 Feb 2013
Stevenson A Lougher L Cumming S Clark D Amirfeyz R
Full Access

The trapeziometacarpal joint (TMJ) is the most commonly involved arthritic joint in the hand and is often injected in the outpatient setting. This study assesses the accuracy of TMJ injections. Six pairs of thawed, fresh-frozen cadaveric upper limbs were placed in the anatomic position. The limbs were randomized to be injected by one of two clinicians (a senior and a junior orthopaedic trainee). The TMJ of these specimens was palpated and injected with 0.5mls aqueous jelly dyed with methylene blue. An independent investigator dissected the specimens and the location of the dye was recorded. A Posterior-Anterior radiograph was then taken to assess the bony anatomy of the joint and graded according to Eaton's classification. Dye was found inside the joint capsule in 10 (83%) of the 12 specimens. Using Fishers Exact test no significant difference was found between the 2 injectors (p=0.46). The 2 joints where the dye was extra-articular had grade III and IV arthritis, whereas all other joints were graded I. This study shows that good accuracy of TMJ injection can be achieved using palpation in the earlier stages of TMJ arthritis, when surface anatomy is accurate enough for an intra-articular injection. This is also when synovitis is more prevalent and injections are more relevant. However the failure rate of injections increases as the disease advances


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXV | Pages 158 - 158
1 Jun 2012
Moussa K
Full Access

Background. The trapeziometacorpal joint (TMJ) of the thumb is a common site of primary osteoarthritis. Pain, crepitis and instability secondary to subluxation are common symptoms associated with TMJ arthritis. Conservative therapy help to control symptoms however with time, many patients progress with pain, deformity and functional limitation. The goals of operative intervention are to restore stability and strength, decrease pain and to provide a functional range of motion. Francobal-prosthesis may fulfil these criterions. Technique. We implanted the prosthesis through a dorso-radial straight longitudinal or slightly curved skin incision. A dorsal capsulotomy is performed and at this step adduction deformity should be addressed. An osteotomy of the proximal surface of the first metacarpal is made perpendicular to the long axis of the medullary cavity followed by reaming of the medullary cavity and then a trial fit. This is followed by preparation of the trapezium including removing any osteophytes, drilling of a cavity. Dental burs may be used at this step to deepen the cavity. The process of cementation started by cementation of the cup with its opening neutral to the joint surface, and if there is any muscle tension, bone is removed from the metacarpal before the metacarpal component is cemented. Reduction is achieved by snapping. The capsule and wound are closed and the thumb is immobilised in an adduction splint for ten days. Results. Results showed marked improvement of pain in many patients with high rate of satisfaction. No restriction of movement or instability was observed. In some cases, loosening of the shaft was noticed. However, this does not affect the overall function. Discussion. De La Caffini`re-prosthesis presents one of the operative options in the management of trapeziometacorpal joint (TMJ). Arthritis, however, this operation is recommended only in selective cases where skaphoid-trapezium-trapezoid (STT) joints are not involved


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXI | Pages 73 - 73
1 May 2012
M.G. S D.J. A P. C A.J. L F.D. B T.R. L
Full Access

Purpose. Osteoarthritis of the trapezio-metacarpal joint (TMJ or basal thumb joint) is a common condition causing significant disability. A range of non-operative and operative management options can be used for its treatment. One of the most common conservative treatments is a steroid injection into the joint. To confirm correct placement of the steroid it is preferable to use X-ray image intensification. Few previous studies have audited effectiveness, particularly with the use of radiological guidance. Methods. This clinical observational study prospectively reviewed the longevity of benefit of steroid injections into the TMJ. They were followed up until the analgesic effects ceased with a questionnaire including visual analogue scores. The clinical improvement was compared with the degree of radiological osteoarthritis (Eaton grade). Seventy-seven patients were recruited with a median age of 62 years and injected with steroid and local anaesthetic under radioscopic guidance. Results. Nearly half of the patients had a 3-month improvement. Two-thirds benefited for at least 2 months. One in six patients had a 6-month benefit, with some patients still improved 2 years after injection. Previously injected patients had a reduced duration of benefit compared to their previous injection. Effectiveness was not affected by Eaton grade. We had no complications except pain during injection. Conclusion. This study demonstrates that there are potentially significant benefits to be gained from steroid injections into the TMJ. We believe the outcome is improved by using radiological guidance and by adding local anaesthetic. Based on this study we recommend steroid injections in all degrees of TMJ osteoarthritis


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 470 - 470
1 Sep 2009
Colombo V Gallo L
Full Access

Animal models have shown that artificially induced temporomandibular joint (TMJ) disc displacement or perforation affect histology and biochemistry of joint cartilage, leading to osteoarthritic changes. However, it is still unclear whether TMJ disc cartilage fails simply due to wear or is degraded by a biological response to mechanical loading. In order to gain insight into TMJ cartilage mechanobiology, a system reproducing the dynamic TMJ compression effects on live tissues was developed. Bovine nasal septum (BNS) cartilage was chosen as a convenient tissue model. However, little information is available in the literature on its material properties. Aim of this study was to determine BNS material properties using a viscoelastic model and verify its suitability as model for TMJ disc cartilage. Cartilage samples were harvested from the central part of BNSs of young, healthy animals. Stress-relaxation tests in unconfined compression were performed on cylindrical plugs samples, obtained by means of biopsy punches. A 10% strain (strain rate 0.01 mm/s) was applied and held for 30 minutes. Stress was estimated from the compressive force data and the initial cross-sectional area. Experimental data were fit to a mathematical model in MATLAB. Experimental results show a highly viscoelastic behavior of the BNS, with a maximum average stress of 0.73 ± 0.14 MPa and relaxed stress of 0.21 ± 0.03 MPa. The numerical model shows good correspondence to the experimental data (R2=0.96). The average values for the instantaneous and relaxed elastic moduli are E0= 7.72 MPa and ER= 2.30 MPa, in the same order of magnitude as the TMJ disc. We conclude that bovine nasal septum can be modeled as viscoelastic tissue and can be used as a first approximation to study mechanobiology of the TMJ disc