The immunoregulatory role of p21 in the development of the temporomandibular joint-osteoarthritis

p21在颞下颌关节骨关节炎发展中的免疫调节作用

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作者:Tsendsuren Khurel-Ochir, Takashi Izawa, Akihiko Iwasa, Fumiya Kano, Akihito Yamamoto, Eiji Tanaka

Conclusions

Our findings indicate that p21 in chondrocytes contributes to regulate matrix synthesis via the control ofm aggrecan and MMP-13 expression under mechanical stress. Thus, p21 might regulate the pathogenesis of osteoarthritis in the TMJ.

Methods

Ten C57BL/6 wild-type (WT) and ten p21-/- mice aged 8 weeks were divided into the untreated and treated groups. In the treated groups, mechanical stress was applied to the temporomandibular joint (TMJ) through forced mouth opening for 3 hr/day for 7 days. The dissected TMJs were assessed using micro-CT, histology, and immunohistochemistry.

Objective

We aimed to identify the immunoregulatory role of the cyclin-dependent kinase inhibitor p21 in the homeostasis of mandibular condylar cartilage affected by mechanical stress. Materials and

Results

Treated p21-/- condyles with mechanical stress revealed more severe subchondral bone destruction, with thinner cartilage layers and smaller proteoglycan area relative to treated WT condyles; untreated WT and p21-/- condyles had smoother surfaces. Immunohistochemistry revealed significant increases in the numbers of caspase-3, interleukin-1β, matrix metalloprotease (MMP)-9, and MMP-13 positive cells, and few aggrecan positive cells, in treated p21-/- than in treated WT samples. Moreover, the number of TUNEL positive cells markedly increased in p21-/- condyles affected by mechanical stress. Conclusions: Our findings indicate that p21 in chondrocytes contributes to regulate matrix synthesis via the control ofm aggrecan and MMP-13 expression under mechanical stress. Thus, p21 might regulate the pathogenesis of osteoarthritis in the TMJ.

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