Department of Orthopaedic Surgery, University of California, San Francisco, 1500 Owens St., San Francisco, CA 94158, USA.
J Orthop Res. 2013 Sep;31(9):1475-83. doi: 10.1002/jor.22382. Epub 2013 May 7.
TGFβ plays a critical role in tendon formation and healing. While its downstream effector Smad3 has been implicated in the healing process, little is known about the role of Smad3 in normal tendon development or tenocyte gene expression. Using mice deficient in Smad3 (Smad3(-/-) ), we show that Smad3 ablation disrupts tendon architecture and has a dramatic impact on normal gene and protein expression during development as well as in mature tendon. In developing and adult tendon, loss of Smad3 results in reduced protein expression of the matrix components Collagen 1 and Tenascin-C. Additionally, when compared to wild type, tendon from adult Smad3(-/-) mice shows a down regulation of key tendon marker genes. Finally, we have established that Smad3 has the ability to physically interact with the critical transcriptional regulators Scleraxis and Mohawk. Together these results indicate a central role for Smad3 in normal tendon formation and in the maintenance of mature tendon.
TGFβ 在肌腱形成和愈合中发挥着关键作用。虽然其下游效应物 Smad3 已被牵涉到愈合过程中，但关于 Smad3 在正常肌腱发育或成纤维细胞基因表达中的作用知之甚少。我们使用 Smad3 缺陷（Smad3(-/-) ）的小鼠表明，Smad3 缺失破坏了肌腱结构，并对发育过程中的正常基因和蛋白质表达以及成熟肌腱产生了巨大影响。在发育中和成年的肌腱中，Smad3 的缺失导致基质成分胶原 1 和腱糖蛋白 C 的蛋白表达减少。此外，与野生型相比，成年 Smad3(-/-) 小鼠的肌腱表现出关键肌腱标记基因的下调。最后，我们已经确定 Smad3 具有与关键转录调节因子 Scleraxis 和 Mohawk 相互作用的能力。这些结果表明 Smad3 在正常肌腱形成和成熟肌腱维持中起着核心作用。
