Involvement of the Scx and Sox9 double-positive cells in the healing process of fibrocartilaginous entheses of supraspinatus following injury in mice

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16628
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kumamoto University
• Principal Investigator: Tokunaga Takuya 熊本大学, 病院, 特任助教 (60759520)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: Scleraxis / Sox9 / enthesis healing / rotator cuff

Outline of Final Research Achievements

Scx+/Sox9+ cells, a specific multipotent cell population, have been shown to contribute to the enthesis formation during mouse embryonic development. We investigated the involvement of Scx+/Sox9+ cells in fibrocartilaginous (FC) enthesis healing using a supraspinatus enthesis healing model established in juvenile (3-week-old) ScxGFP Tg mice. In juvenile mice, Scx+/Sox9+ cells were widely distributed in injury site in early phase, and they were located near the surface of the repaired FC at 4 week post-injury. The spatiotemporal localization pattern of Scx+/Sox9+ cells in juvenile mice was similar to that in postnatal FC enthesis formation. These findings indicate that Scx+/Sox9+ cells may be able to act as entheseal progenitors in postnatal healing. Moreover, their healing action may be related to the TGF-beta/pSmad3 pathway, as evidenced by the higher pSmad3-positive cell count during healing.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

Scx+/Sox9+前駆細胞は発生期に腱・靱帯の付着部の形成に寄与することが示されている。本研究では, 幼若マウスの腱板付着部損傷後の線維軟骨層の修復にScx+/Sox9+細胞が寄与ししている可能性を示唆させる結果を得た。これは, 内在性のScx+/Sox9+細胞の修復部への動員が線維軟骨修復に関連する可能性性を示唆する結果であり, 成体におけるScx+/Sox9+細胞を介した新たな修復促進治療につながる知見となることが期待される。