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

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 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 h/day for 7 days. The dissected TMJs were assessed using micro-CT, histology, and immunohistochemistry.
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.
Conclusion: Our findings indicate that p21 in chondrocytes contributes to regulate matrix synthesis via the control of aggrecan and MMP-13 expression under mechanical stress. Thus, p21 might regulate the pathogenesis of osteoarthritis in the TMJ.

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本論文は，著者Tsendsuren Khurel-Ochirの学位論文として提出され，学位審査・授与の対象となっている。

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