Developmental and Regenerative Biology, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.
Division of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, Hong Kong.
Elife. 2017 Dec 15;6:e30474. doi: 10.7554/eLife.30474.
Both extrinsic and intrinsic tissues contribute to tendon repair, but the origin and molecular functions of extrinsic tissues in tendon repair are not fully understood. Here we show that tendon sheath cells harbor stem/progenitor cell properties and contribute to tendon repair by activating Hedgehog signaling. We found that () can be used as an adult tendon-sheath-specific marker in mice. Lineage tracing experiments show that -expressing cells in adult sheath tissues possess clonogenic and multipotent properties comparable to those of stem/progenitor cells isolated from tendon fibers. Transplantation of sheath tissues improves tendon repair. Mechanistically, Hh signaling in sheath tissues is necessary and sufficient to promote the proliferation of -expressing cells in sheath tissues, and its action is mediated through TGFβ/Smad3 signaling. Furthermore, co-localization of GLI1 and MKX cells is also found in human tendinopathy specimens. Our work reveals the molecular function of Hh signaling in extrinsic sheath tissues for tendon repair.
外在组织和内在组织都有助于肌腱修复，但外在组织在肌腱修复中的起源和分子功能还不完全清楚。在这里，我们表明，腱鞘细胞具有干细胞/祖细胞特性，并通过激活 Hedgehog 信号通路促进肌腱修复。我们发现 () 可作为小鼠成年腱鞘组织特异性标志物。谱系追踪实验表明，成年鞘组织中表达的细胞具有与从肌腱纤维中分离出的干细胞/祖细胞相当的克隆形成和多能性。鞘组织的移植可改善肌腱修复。在机制上，鞘组织中的 Hh 信号对于促进鞘组织中表达的细胞的增殖是必要且充分的，其作用是通过 TGFβ/Smad3 信号传导介导的。此外，在人类肌腱病标本中也发现了 GLI1 和 MKX 细胞的共定位。我们的工作揭示了 Hedgehog 信号在外在鞘组织中对肌腱修复的分子功能。
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