Nayak Pavan K, Subramanian Arul, Schilling Thomas F
Department of Developmental and Cell Biology, University of California, Irvine, United States.
Elife. 2025 Mar 27;14:e105802. doi: 10.7554/eLife.105802.
Mechanical forces play a critical role in tendon development and function, influencing cell behavior through mechanotransduction signaling pathways and subsequent extracellular matrix (ECM) remodeling. Here, we investigate the molecular mechanisms by which tenocytes in developing zebrafish embryos respond to muscle contraction forces during the onset of swimming and cranial muscle activity. Using genome-wide bulk RNA sequencing of FAC-sorted tenocytes we identify novel tenocyte markers and genes involved in tendon mechanotransduction. Embryonic tendons show dramatic changes in expression of (), (), and the transcription factor (), as muscles start to contract. Using embryos paralyzed either by loss of muscle contractility or neuromuscular stimulation we confirm that muscle contractile forces influence the spatial and temporal expression patterns of all three genes. Quantification of these gene expression changes across tenocytes at multiple tendon entheses and myotendinous junctions reveals that their responses depend on force intensity, duration, and tissue stiffness. These force-dependent feedback mechanisms in tendons, particularly in the ECM, have important implications for improved treatments of tendon injuries and atrophy.
机械力在肌腱发育和功能中起着关键作用，通过机械转导信号通路影响细胞行为以及随后的细胞外基质（ECM）重塑。在此，我们研究了发育中的斑马鱼胚胎中的肌腱细胞在游泳开始和头部肌肉活动期间对肌肉收缩力作出反应的分子机制。通过对荧光激活细胞分选（FACS）分离的肌腱细胞进行全基因组大量RNA测序，我们确定了参与肌腱机械转导的新型肌腱细胞标记物和基因。随着肌肉开始收缩，胚胎肌腱在（）、（）和转录因子（）的表达上出现显著变化。利用因肌肉收缩力丧失或神经肌肉刺激而瘫痪的胚胎，我们证实肌肉收缩力会影响这三个基因的时空表达模式。对多个肌腱附着点和肌腱-肌肉连接处的肌腱细胞中这些基因表达变化的定量分析表明，它们的反应取决于力的强度、持续时间和组织硬度。肌腱中这些力依赖性反馈机制，尤其是在细胞外基质中的机制，对改善肌腱损伤和萎缩的治疗具有重要意义。
