Liu Yang, Xu Jia, Xu Liangliang, Wu Tianyi, Sun Yuxin, Lee Yuk-Wai, Wang Bin, Chan Hsiao-Chang, Jiang Xiaohua, Zhang Jinfang, Li Gang
Department of Orthopaedics and Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Special Administrative Region, China.
Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
FASEB J. 2017 Sep;31(9):3800-3815. doi: 10.1096/fj.201601181R. Epub 2017 May 11.
Tendons are a mechanosensitive tissue, which enables them to transmit to bone forces that are derived from muscle. Patients with tendon injuries, such as tendinopathy or tendon rupture, were often observed with matrix degeneration, and the healing of tendon injuries remains a challenge as a result of the limited understanding of tendon biology. Our study demonstrates that the stretch-mediated activation channel, cystic fibrosis transmembrane conductance regulator (CFTR), was up-regulated in tendon-derived stem cells (TDSCs) during tenogenic differentiation under mechanical stretching. Tendon tissues in CFTR-dysfunctional DF508 mice exhibited irregular cell arrangement, uneven fibril diameter distribution, weak mechanical properties, and less matrix formation in a tendon defect model. Moreover, both tendon tissues and TDSCs isolated from DF508 mice showed significantly decreased levels of tendon markers, such as , , (collagen type I α 1 chain), and Furthermore, by RNA sequencing analysis, we demonstrated that Wnt/β-catenin signaling was abnormally activated in TDSCs from DF508 mice, thereby further activating the pERK1/2 signaling pathway. Of most importance, we found that intervention in pERK1/2 signaling could promote tenogenic differentiation and tendon regeneration both and Taken together, our study demonstrates that CFTR plays an important role in tenogenic differentiation and tendon regeneration by inhibiting the β-catinin/pERK1/2 signaling pathway. The therapeutic strategy of intervening in the CFTR/β-catenin/pERK1/2 regulatory axis may be helpful for accelerating tendon injury healing, which has implications for tendon injury management.-Liu, Y., Xu, J., Xu, L., Wu, T., Sun, Y., Lee, Y.-W., Wang, B., Chan, H.-C., Jiang, X., Zhang, J., Li, G. Cystic fibrosis transmembrane conductance regulator mediates tenogenic differentiation of tendon-derived stem cells and tendon repair: accelerating tendon injury healing by intervening in its downstream signaling.
肌腱是一种机械敏感组织，使其能够将源自肌肉的力量传递至骨骼。患有肌腱损伤（如肌腱病或肌腱断裂）的患者常出现基质退变，由于对肌腱生物学的了解有限，肌腱损伤的愈合仍然是一项挑战。我们的研究表明，在机械拉伸下的成腱分化过程中，拉伸介导的激活通道——囊性纤维化跨膜传导调节因子（CFTR）在肌腱来源的干细胞（TDSCs）中上调。在肌腱缺损模型中，CFTR功能失调的DF508小鼠的肌腱组织表现出细胞排列不规则、纤维直径分布不均、力学性能较弱以及基质形成较少。此外，从DF508小鼠分离的肌腱组织和TDSCs均显示肌腱标志物（如 、 、I型胶原α1链）的水平显著降低。此外，通过RNA测序分析，我们证明Wnt/β-连环蛋白信号在DF508小鼠的TDSCs中异常激活，从而进一步激活pERK1/2信号通路。最重要的是，我们发现干预pERK1/2信号可促进体内外的成腱分化和肌腱再生。综上所述，我们的研究表明CFTR通过抑制β-连环蛋白/pERK1/2信号通路在成腱分化和肌腱再生中发挥重要作用。干预CFTR/β-连环蛋白/pERK1/2调节轴的治疗策略可能有助于加速肌腱损伤愈合，这对肌腱损伤的管理具有重要意义。——刘，Y.，徐，J.，徐，L.，吴，T.，孙，Y.，李，Y.-W.，王，B.，陈，H.-C.，江，X.，张，J.，李，G. 囊性纤维化跨膜传导调节因子介导肌腱来源干细胞的成腱分化和肌腱修复：通过干预其下游信号加速肌腱损伤愈合
