McKay Orthopedic Research Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA.
University of South Florida, Morsani College of Medicine, Tampa, FL 33612, USA.
J Biomech. 2022 Nov;144:111315. doi: 10.1016/j.jbiomech.2022.111315. Epub 2022 Sep 30.
Tendon function is dependent on proper organization and maintenance of the collagen I tissue matrix. Collagen V is a critical regulator of collagen I fibrils, and while prior studies have shown a negative impact of collagen V deficiency on tendon healing outcomes, these studies are confounded by collagen V deficiency through tendon development. The specific role of collagen V in regulating healing tendon properties is therefore unknown. By using inducible Col5a1 knockdown models and analyzing gene expression, fibril and histological tendon morphology, and tendon mechanical properties, this study defines the isolated role of collagen V through tendon healing. Patellar tendon injury caused large changes in tendon gene expression, and Col5a1 knockdown resulted in dysregulated expression of several genes through tendon healing. Col5a1 knockdown also impacted collagen fibril size and shape without observable changes in scar tissue formation. Surprisingly, heterozygous Col5a1 knockdown resulted in improved stiffness of healing tendons that was not observed with homozygous Col5a1 knockdown. Together, these results present an unexpected and dynamic role of collagen V deficiency on tendon healing outcomes following injury. This work suggests a model of tendon healing in which quasi-static mechanics may be improved through titration of collagen fibril size and shape with modulation of collagen V expression and activity.
肌腱功能取决于胶原 I 组织基质的适当组织和维持。胶原 V 是胶原 I 原纤维的关键调节因子，尽管先前的研究表明胶原 V 缺乏对肌腱愈合结果有负面影响，但这些研究受到了肌腱发育过程中胶原 V 缺乏的干扰。因此，胶原 V 在调节愈合肌腱特性方面的具体作用尚不清楚。本研究通过使用诱导性 Col5a1 敲低模型和分析基因表达、原纤维和组织学肌腱形态以及肌腱力学特性，定义了胶原 V 在肌腱愈合过程中的独立作用。髌腱损伤导致肌腱基因表达发生巨大变化，Col5a1 敲低导致肌腱愈合过程中几个基因的表达失调。Col5a1 敲低还影响胶原纤维大小和形状，但未观察到瘢痕组织形成的变化。令人惊讶的是，杂合子 Col5a1 敲低导致愈合肌腱硬度增加，而纯合子 Col5a1 敲低则没有观察到这种情况。综上所述，这些结果呈现了胶原 V 缺乏对损伤后肌腱愈合结果的出乎意料和动态作用。这项工作提出了一种肌腱愈合模型，其中准静态力学可能通过调节胶原 V 的表达和活性来改善胶原纤维大小和形状的滴定来改善。
