Lin28a 过表达揭示了 Erk 信号在关节软骨发育中的作用。
Lin28a overexpression reveals the role of Erk signaling in articular cartilage development.
机构信息
Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
出版信息
Development. 2018 Aug 2;145(15):dev162594. doi: 10.1242/dev.162594.
Adult articular cartilage shows limited tissue turnover, and therefore development of the proper structure of articular cartilage is crucial for life-long joint function. However, the mechanism by which the articular cartilage structure is developmentally regulated is poorly understood. In this study, we show evidence that activation of extracellular signal-regulated kinases (Erk1/2) in articular chondrocyte progenitors during developmental stages control articular cartilage thickness. We found that overexpression of Lin28a, an RNA-binding protein that regulates organismal growth and metabolism, in articular chondrocyte progenitor cells upregulated Erk signaling and increased articular cartilage thickness. Overexpression of a constitutively active Kras mimicked Lin28a overexpression, and inhibition of Erk signaling during embryonic stages normalized the cartilage phenotype of both Kras- and Lin28a-overexpressing mice. These results suggest that articular cartilage thickness is mainly determined during the process of embryonic synovial joint development, which is positively regulated by Erk signaling.
成人关节软骨组织更新能力有限，因此，关节软骨的适当结构的发育对于终身关节功能至关重要。然而，关节软骨结构如何在发育过程中受到调控的机制尚不清楚。在这项研究中，我们提供了证据表明，在发育阶段，细胞外信号调节激酶（Erk1/2）在关节软骨细胞前体细胞中的激活控制着关节软骨的厚度。我们发现，在关节软骨细胞前体细胞中过表达 Lin28a（一种调节机体生长和代谢的 RNA 结合蛋白）可上调 Erk 信号通路并增加关节软骨厚度。过表达组成型激活的 Kras 可模拟 Lin28a 的过表达，而在胚胎阶段抑制 Erk 信号通路可使 Kras 和 Lin28a 过表达的小鼠的软骨表型正常化。这些结果表明，关节软骨厚度主要在胚胎滑膜关节发育过程中决定，Erk 信号通路正向调节关节软骨厚度。
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