Research Division, Shriners Hospital for Children, Portland, Oregon, USA.
Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Stem Cells Dev. 2021 Jun 1;30(11):601-609. doi: 10.1089/scd.2020.0209. Epub 2021 Apr 27.
An efficient musculoskeletal system depends on the precise assembly and coordinated growth and function of muscles, skeleton, and tendons. However, the mechanisms that drive integrated musculoskeletal development and coordinated growth and differentiation of each of these tissues are still being uncovered. Epigenetic modifiers have emerged as critical regulators of cell fate differentiation, but so far almost nothing is known about their roles in tendon biology. Previous studies have shown that epigenetic modifications driven by Enhancer of zeste homolog 2 (EZH2), a major histone methyltransferase, have significant roles in vertebrate development including skeletal patterning and bone formation. We now find that targeting through the limb mesenchyme also has significant effects on tendon and muscle patterning, likely reflecting the essential roles of early mesenchymal cues mediated by for coordinated patterning and development of all tissues of the musculoskeletal system. Conversely, loss of in the tendon cells did not disrupt overall tendon structure or collagen organization suggesting that tendon differentiation and maturation are independent of signaling.
一个高效的运动系统依赖于肌肉、骨骼和肌腱的精确组装以及协调生长和功能。然而，驱动运动系统的整体发育以及这些组织的协调生长和分化的机制仍在探索之中。表观遗传修饰因子已成为细胞命运分化的关键调节因子，但迄今为止，人们对它们在肌腱生物学中的作用几乎一无所知。先前的研究表明，由增强子结合蛋白 2（EZH2）驱动的表观遗传修饰在脊椎动物发育中具有重要作用，包括骨骼模式形成和骨形成。我们现在发现，通过肢间充质靶向 也会对肌腱和肌肉模式形成产生显著影响，这可能反映了由 介导的早期间充质信号在协调运动系统所有组织的模式形成和发育中的重要作用。相反，在肌腱细胞中缺失 并不会破坏整个肌腱结构或胶原组织，这表明肌腱分化和成熟不依赖于 信号。
