Exploratory research for tendon injury therapy targeting tissue fibrosis and heterotopic ossification

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17999
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Hiroshima University
• Principal Investigator: Ikuta Yasunari 広島大学, 病院(医), 助教 (50856086)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腱修復 / 線維化 / 異所性骨化 / マウスアキレス腱損傷モデル

Outline of Final Research Achievements

In the Achilles tendon injury model, scar formation and heterotopic ossification (HO) were observed during tendon repair. Tendon tissue-specific Dicer gene-deficient mice showed even more significant reduction in tendon repair ability. Local administration of a retinoic acid receptor agonist (RARA) targeting scar formation and HO in Achilles tendon injury model resulted in histologically favorable tendon repair. Furthermore, in vitro experiments using isolated tendon-derived fibroblasts, RARA inhibited cartilage differentiation and cytokine expression. Thus, RARA was shown to promote tendon repair in a mouse Achilles tendon injury model.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

腱修復過程における瘢痕形成、異所性骨化は修復腱の強度を低下させ、再断裂のリスクとなるが、これらを直接標的とした腱修復治療はこれまで確立されていなかった。本研究は、腱修復過程の瘢痕形成、異所性骨化に関連する分子機構の一部を明らかにした。さらにレチノイン酸受容体アゴニストの腱修復過程における瘢痕化や異所性骨化の抑制効果を介した腱修復の促進効果を明らかにした。腱の線維化や異所性骨化を標的とした腱損傷に対する新たな治療法への応用が期待できる。