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

Abstract

Abstract 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 hr/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. 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.

Keywords

• chondrocyte
• metalloprotease
• osteoarthritis
• p21
• temporomandibular joint