Temporomandibular joint damage in K/BxN arthritic mice

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.

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“…Quantitative μCT analyses were performed using a Skyscan scanner 1276 μCT system (Bruker, Belgium) as previously described. 24 , 44 , 48 …”

Section: Methodsmentioning

confidence: 99%

Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice

Lai

Zheng

et al. 2022

Int J Oral Sci

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“…In another study using the K/BxN model of spontaneous inflammation, increased expression of vascular endothelial growth factor and IL-17 and decreased expression of osteoprotegerin were observed in the limb joints, but not in the TMJ ( 25 ). In the same study with the K/BxN mouse model, the enlargement of the upper joint cavity in arthritic mice was confirmed by Magnetic Resonance Imaging, and only cartilage detachment of the TMJ surface was observed ( 26 ). In the present study, although the CAIA group showed increased osteoclast differentiation, there was no significant thinning of the chondrocyte layer or localization of lymphocytes.…”

Section: Discussionmentioning

confidence: 81%

Overload of the Temporomandibular Joints Accumulates γδ T Cells in a Mouse Model of Rheumatoid Arthritis: A Morphological and Histological Evaluation

et al. 2022

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Recently, it has been reported that γδ T cells are associated with the pathology of rheumatoid arthritis (RA). However, there are many uncertainties about their relationship. In this study, we investigated the morphological and histological properties of peripheral as well as temporomandibular joints (TMJ) in a mouse model of rheumatoid arthritis with and without exposure to mechanical strain on the TMJ. Collagen antibody-induced arthritis (CAIA) was induced by administering collagen type II antibody and lipopolysaccharide to male DBA/1JNCrlj mice at 9−12 weeks of age, and mechanical stress (MS) was applied to the mandibular condyle. After 14 days, 3D morphological evaluation by micro-CT, histological staining (Hematoxylin Eosin, Safranin O, and Tartrate-Resistant Acid Phosphatase staining), and immunohistochemical staining (ADAMTS-5 antibody, CD3 antibody, CD45 antibody, RORγt antibody, γδ T cell receptor antibody) were performed. The lower jawbone was collected. The mandibular condyle showed a rough change in the surface of the mandibular condyle based on three-dimensional analysis by micro-CT imaging. Histological examination revealed bone and cartilage destruction, such as a decrease in chondrocyte layer width and an increase in the number of osteoclasts in the mandibular condyle. Then, immune-histological staining revealed accumulation of T and γδ T cells in the subchondral bone. The temporomandibular joint is less sensitive to the onset of RA, but it has been suggested that it is exacerbated by mechanical stimulation. Additionally, the involvement of γδ T cells was suggested as the etiology of rheumatoid arthritis.

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“…In another study using the K/BxN model of spontaneous in ammation, increased expression of vascular endothelial growth factor and IL-17, and decreased expression of osteoprotegerin were observed in the limb joints, but not in the TMJ (23). In the same study with the K/BxN mouse model, the enlargement of the upper joint cavity in arthritic mice was con rmed by Magnetic Resonance Imaging, and only cartilage detachment of the TMJ surface was observed (24). In the present study, although the CAIA group showed increased osteoclast differentiation, there was no signi cant thinning of the chondrocyte layer or localization of lymphocytes.…”

Section: Effects Of Excessive Ms On the Mandibular Condyle In The Caia Mouse Modelmentioning

confidence: 83%

Effect of Mechanical Stress on Rheumatoid Arthritis of the Temporomandibular Joint: a Morphological and Histological Evaluation

Nagai

Ishii

Nishii

2021

Preprint

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Background Rheumatoid arthritis of the temporomandibular joint (TMJ-RA) has been reported to have a larger incidence range than systemic rheumatoid arthritis (RA). The presence or absence of mechanical stress (MS) is considered a factor in this. In this study, we hypothesized that TMJ-RA develops or worsens when excessive MS is applied to the temporomandibular joint of RA mouse models. We aimed to clarify the relationship between TMJ-RA and MS through morphological and histological evaluation. Methods Collagen antibody-induced arthritis (CAIA) was induced in male DBA/1JNCrlj 9–12 weeks old mice by administering Type II collagen antibody and lipopolysaccharide to produce RA model mice. MS was applied to the mandibular condyle. The group was separated into non-RA (control group (N = 5) and MS group (N = 5)), and RA group (CAIA group (N = 5)and CAIA MS group (N = 5)). To confirm the morphological changes in the mandibular condyle, micro-CT imaging was performed. Histological evaluation of the TMJ was performed by hematoxylin and eosin staining for condylar cartilage cell layer thickness, Safranin O staining for proteoglycans, and tartrate-resistant acidic phosphatase staining for osteoclast count. Immunohistochemical evaluation was performed to assess the localization of cartilage destruction enzymes using ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs) antibody. Additionally, CD3 (cluster of differentiation), CD45, and γδ TCR (T cell receptor) antibodies were used to localize and identify the type of lymphocytes. Results In the CAIA MS model, a three-dimensional analysis of the temporomandibular joint by microcomputer tomography showed a crude change in the surface of the mandibular condyle. Histological examination revealed a decrease in the chondrocyte layer width and an increase in the number of osteoclasts in the mandibular condyle. T cell accumulation was observed, and γδ T cell involvement was confirmed. Conclusions In the CAIA model, the TMJ was less sensitive to the initiation of RA. However, the results suggested that it was exacerbated by MS, and that γδ T cells may be involved in TMJ-RA.

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Temporomandibular joint damage in K/BxN arthritic mice

Cited by 13 publications

References 36 publications

Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice

Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice

Overload of the Temporomandibular Joints Accumulates γδ T Cells in a Mouse Model of Rheumatoid Arthritis: A Morphological and Histological Evaluation

Effect of Mechanical Stress on Rheumatoid Arthritis of the Temporomandibular Joint: a Morphological and Histological Evaluation

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