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2019 Fiscal Year Final Research Report

Regulatory system of microRNA and ADAM12 expression in the process of joint remodeling

Research Project

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Project/Area Number 17K11010
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionOkayama University

Principal Investigator

Nishida Keiichiro  岡山大学, 医歯薬学総合研究科, 准教授 (80284058)

Co-Investigator(Kenkyū-buntansha) 大月 孝志  岡山大学, 保健学研究科, 非常勤研究員 (10534802)
廣畑 聡  岡山大学, 保健学研究科, 教授 (90332791)
Project Period (FY) 2017-04-01 – 2020-03-31
Keywords軟骨代謝 / miRNA / 疾患修飾性OA治療薬 / メカニカルストレス / エピジェネティクス / ADAM12
Outline of Final Research Achievements

Adam12 was upregulated prior to Col10a1 during chondrogenic differentiation in wild-type ATDC5 cells. In Adam12-KO ATDC5 cells, following initiation of chondrogenic differentiation, we observed a reduction in Igf-1 expression along with an upregulation of hypertrophy-associated Runx2, Col10a1, and type X collagen protein expressions. In ATDC5 wild-type cells, stimulation with TGF-β1 upregulated the expressions of Adam12 and Igf-1 and downregulated the expression of Runx2. In contrast, in Adam12-KO ATDC5 cells, these TGF-β1-induced changes were suppressed. Adam12 overexpression resulted in an upregulation of Igf-1 and downregulation of Runx2 expression in ATDC5 cells. The findings suggest that ADAM12 has important role in the regulation of chondrocyte differentiation, potentially by regulation of TGF-β1-dependent signaling and that targeting of ADAM12 may have a role in management of abnormal chondrocyte differentiation.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、軟骨細胞において、ADAM12がTGF-β依存性シグナルに関与し、肥大化に関連するRUNX2およびX型コラーゲン発現を抑制することで軟骨細胞分化を調節していることを示した。また、我々は, ヒトから採取した変形性関節症の骨棘組織において, 増殖期~肥大期の軟骨細胞にADAM12が局在することを突き止めている。このことは、ADAM12が変形性関節症の骨棘形成や関節リウマチにおける骨関節のリモデリングに関与していることを示唆する。また、miR-29bの人為的制御によって、ADAM12の発現が制御可能である可能性も示された。

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Published: 2021-02-19  

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