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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. 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. 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. Results. UAC altered the histological structure and extracellular matrix content of cartilage in the temporomandibular joint (TMJ), and KO of MiR21 alleviated this effect (p < 0.05). Upregulation of MiR21 influenced the expression of TMJ-OA related molecules in mandibular condylar chondrocytes via targeting Gdf5 (p < 0.05). Gdf5 overexpression significantly decreased matrix metalloproteinase 13 (MMP13) expression (p < 0.05) and reversed the effects of MiR21 (p < 0.05). Conclusion. MiR21, which acts as a critical regulator of Gdf5 in chondrocytes, regulates TMJ-OA related molecules and is involved in cartilage matrix degradation, contributing to the progression of TMJ-OA. Cite this article: Bone Joint Res 2020;9(10):689–700


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. 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.


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1216 - 1222
1 Nov 2024
Castagno S Gompels B Strangmark E Robertson-Waters E Birch M van der Schaar M McCaskie AW

Aims

Machine learning (ML), a branch of artificial intelligence that uses algorithms to learn from data and make predictions, offers a pathway towards more personalized and tailored surgical treatments. This approach is particularly relevant to prevalent joint diseases such as osteoarthritis (OA). In contrast to end-stage disease, where joint arthroplasty provides excellent results, early stages of OA currently lack effective therapies to halt or reverse progression. Accurate prediction of OA progression is crucial if timely interventions are to be developed, to enhance patient care and optimize the design of clinical trials.

Methods

A systematic review was conducted in accordance with PRISMA guidelines. We searched MEDLINE and Embase on 5 May 2024 for studies utilizing ML to predict OA progression. Titles and abstracts were independently screened, followed by full-text reviews for studies that met the eligibility criteria. Key information was extracted and synthesized for analysis, including types of data (such as clinical, radiological, or biochemical), definitions of OA progression, ML algorithms, validation methods, and outcome measures.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 439 - 452
13 Jul 2022
Sun Q Li G Liu D Xie W Xiao W Li Y Cai M

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.


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).


The Bone & Joint Journal
Vol. 103-B, Issue 8 | Pages 1380 - 1385
2 Aug 2021
Kim Y Ryu J Kim JK Al-Dhafer BAA Shin YH

Aims

The aim of this study was to assess arthritis of the basal joint of the thumb quantitatively using bone single-photon emission CT/CT (SPECT/CT) and evaluate its relationship with patients’ pain and function.

Methods

We retrospectively reviewed 30 patients (53 hands) with symptomatic basal joint arthritis of the thumb between April 2019 and March 2020. Visual analogue scale (VAS) scores for pain, grip strength, and pinch power of both hands and Patient-Rated Wrist/Hand Evaluation (PRWHE) scores were recorded for all patients. Basal joint arthritis was classified according to the modified Eaton-Glickel stage using routine radiographs and the CT scans of SPECT/CT, respectively. The maximum standardized uptake value (SUVmax) from SPECT/CT was measured in the four peritrapezial joints and the highest uptake was used for analysis.


The Bone & Joint Journal
Vol. 101-B, Issue 3 | Pages 272 - 280
1 Mar 2019
Verspoor FGM Mastboom MJL Hannink G van der Graaf WTA van de Sande MAJ Schreuder HWB

Aims

The aim of this study was to evaluate health-related quality of life (HRQoL) and joint function in tenosynovial giant cell tumour (TGCT) patients before and after surgical treatment.

Patients and Methods

This prospective cohort study run in two Dutch referral centres assessed patient-reported outcome measures (PROMs; 36-Item Short-Form Health Survey (SF-36), visual analogue scale (VAS) for pain, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) in 359 consecutive patients with localized- and diffuse-type TGCT of large joints. Patients with recurrent disease (n = 121) and a wait-and-see policy (n = 32) were excluded. Collected data were analyzed at specified time intervals preoperatively (baseline) and/or postoperatively up to five years.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 11 | Pages 1448 - 1454
1 Nov 2012
Ng CY Watts AC

Bone loss involving articular surface is a challenging problem faced by the orthopaedic surgeon. In the hand and wrist, there are articular defects that are amenable to autograft reconstruction when primary fixation is not possible. In this article, the surgical techniques and clinical outcomes of articular reconstructions in the hand and wrist using non-vascularised osteochondral autografts are reviewed.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 1 | Pages 111 - 114
1 Jan 2011
Iwai S Sato K Nakamura T Okazaki M Itoh Y Toyama Y Ikegami H

We present a case of post-traumatic osteonecrosis of the radial head in a 13-year-old boy which was treated with costo-osteochondral grafts. A satisfactory outcome was seen at a follow-up of two years and ten months.

Although costo-osteochondral grafting has been used in the treatment of defects in articular cartilage, especially in the hand and the elbow, the extension of the technique to manage post-traumatic osteonecrosis of the radial head in a child has not previously been reported in the English language literature. Complete relief of pain was obtained and an improvement in the range of movement was observed. The long-term results remain uncertain.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 4 | Pages 533 - 535
1 Apr 2009
Hamilton LC Biant LC Temple LN Field RE

Idiopathic calcium pyrophosphate deposition disease (pseudogout) has a variable presentation. Many joints are usually affected; single joint disease is uncommon. We present a case report of primary monoarticular pseudogout affecting the hip. The diagnosis was made on the appearance and analysis of specimens obtained at arthroscopy. Monoarticular pseudogout is rare, but should be considered in the differential diagnosis of any presentation of joint pain.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 11 | Pages 1504 - 1508
1 Nov 2007
Bhadra AK Pollock R Tirabosco RP Skinner JAM Cannon SR Briggs TWR Flanagan AM

Four patients who developed malignant synovial tumours are described; one with chondromatosis developed a synovial chondrosarcoma and three with pigmented villonodular synovitis developed malignant change. The relevant literature is discussed.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 2 | Pages 196 - 201
1 Feb 2007
Veitch S Blake SM David H

We prospectively reviewed 14 patients with deficiency of the proximal pole of the scaphoid who were treated by rib osteochondral replacement arthroplasty.

Improvement in wrist function occurred in all except one patient with enhanced grip strength, less pain and maintenance of wrist movement. In 13 patients wrist function was rated as good or excellent according to the modified wrist function score of Green and O’Brien. The mean pre-operative score of 54 (35 to 80) rose to 79 (50 to 90) at review at a mean of 64 months (27 to 103). Carpal alignment did not deteriorate in any patient and there were no cases of nonunion or significant complications.

This procedure can restore the mechanical integrity of the proximal pole of the scaphoid satisfactorily and maintain wrist movement while avoiding the potential complications of alternative replacement arthroplasty techniques and problems associated with vascularised grafts and salvage techniques.