Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Stem Cells Transl Med. 2022 Jul 20;11(7):715-726. doi: 10.1093/stcltm/szac027.
The tendon enthesis plays a critical role in facilitating movement and reducing stress within joints. Partial enthesis injuries heal in a mechanically inferior manner and never achieve healthy tissue function. The cells responsible for tendon-to-bone healing remain incompletely characterized and their origin is unknown. Here, we evaluated the putative role of mouse skeletal stem cells (mSSCs) in the enthesis after partial-injury. We found that mSSCs were present at elevated levels within the enthesis following injury and that these cells downregulated TGFβ signaling pathway elements at both the RNA and protein levels. Exogenous application of TGFβ post-injury led to a reduced mSSC response and impaired healing, whereas treatment with a TGFβ inhibitor (SB43154) resulted in a more robust mSSC response. Collectively, these data suggest that mSSCs may augment tendon-to-bone healing by dampening the effects of TGFβ signaling within the mSSC niche.
腱骨结合部在促进关节运动和减轻关节内压力方面起着关键作用。部分腱骨结合部损伤以机械性能较差的方式愈合，且永远无法恢复健康组织的功能。负责腱骨愈合的细胞特征仍不完全明确，其来源也未知。在这里，我们评估了小鼠骨骼干细胞（mSSC）在部分损伤后的腱骨结合部中的潜在作用。我们发现，损伤后腱骨结合部中的 mSSC 水平升高，这些细胞在 RNA 和蛋白质水平下调 TGFβ 信号通路元件。损伤后外源性应用 TGFβ 会导致 mSSC 反应减少和愈合受损，而用 TGFβ 抑制剂（SB43154）治疗则会导致更强烈的 mSSC 反应。综上所述，这些数据表明，mSSC 可能通过在 mSSC 龛内抑制 TGFβ 信号的作用来增强腱骨愈合。
