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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)313-322
Number of pages10
JournalClinical and Experimental Dental Research
Volume7
Issue number3
DOIs
Publication statusPublished - Jun 2021
Externally publishedYes

Keywords

  • chondrocyte
  • metalloprotease
  • osteoarthritis
  • p21
  • temporomandibular joint

ASJC Scopus subject areas

  • Dentistry(all)

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