Mechanism of osteophyte formation in osteoarthritis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20055
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Okayama University
• Principal Investigator: Horita Masahiro 岡山大学, 医学部, 客員研究員 (00708084)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 軟骨細胞分化 / ADAM12 / IGF-1 / RUNX2 / Type X collagen

Outline of Final Research Achievements

ADAM12 was identified in chondrocytes of the proliferative and hypertrophic zones in mouse growth plates by immunohistochemistry. 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.

Free Research Field

外科系臨床医学・整形外科

Academic Significance and Societal Importance of the Research Achievements

変形性関節症 (OA) は加齢とともに罹患率が増加することから、高齢化するわが国において患者数は今後ますます増えることが予想されている。しかし、OA軟骨変性の進行や骨棘形成に関与している内軟骨性骨化の機序はいまだ明らかになっていない。本研究結果より、内軟骨性骨化の過程においてADAM12が重要な役割をすることが示唆された。この分子が治療標的となり、OAの病態解明や症状緩和の一助になる可能性があり社会的意義は高いと考える。