Tendon injuries are a major clinical problem, with poor patient outcomes caused by abundant scar tissue deposition during healing. Myofibroblasts play a critical role in the initial restoration of structural integrity after injury. However, persistent myofibroblast activity drives the transition to fibrotic scar tissue formation. As such, disrupting myofibroblast persistence is a key therapeutic target. While myofibroblasts are typically defined by the presence of αSMA+ stress fibers, αSMA is expressed in other cell types including the vasculature. As such, modulation of myofibroblast dynamics via disruption of αSMA expression is not a translationally tenable approach. Recent work has demonstrated that Periostin-lineage (Postn^Lin) cells are a precursor for cardiac fibrosis-associated myofibroblasts. In contrast to this, here we show that Postn^Lin cells contribute to a transient αSMA+ myofibroblast population that is required for functional tendon healing, and that Periostin forms a supportive matrix niche that facilitates myofibroblast differentiation and persistence. Collectively, these data identify the Periostin matrix niche as a critical regulator of myofibroblast fate and persistence that could be targeted for therapeutic manipulation to facilitate regenerative tendon healing.

肌腱损伤是一个主要的临床问题，愈合过程中大量疤痕组织沉积导致患者预后不佳。肌成纤维细胞在损伤后结构完整性的初步恢复中发挥着关键作用。然而，持续的肌成纤维细胞活性驱动向纤维化疤痕组织形成的转变。因此，破坏肌成纤维细胞的持久性是一个关键的治疗目标。虽然肌成纤维细胞通常由 αSMA+ 应力纤维的存在来定义，但 αSMA 在包括脉管系统在内的其他细胞类型中表达。因此，通过破坏 αSMA 表达来调节肌成纤维细胞动力学并不是一种可转化的方法。最近的工作表明，Periostin 谱系 (Postn ^Lin ) 细胞是心脏纤维化相关肌成纤维细胞的前体。与此相反，这里我们表明 Postn ^Lin 细胞有助于功能性肌腱愈合所需的短暂 αSMA+ 肌成纤维细胞群，并且 Periostin 形成支持性基质生态位，促进肌成纤维细胞分化和持久性。总的来说，这些数据表明骨膜素基质生态位是肌成纤维细胞命运和持久性的关键调节因子，可以作为治疗操作的目标，以促进再生肌腱愈合。