School of Medicine, Deakin University, Waurn Ponds, Victoria 3216, Australia.
Centre for Molecular and Medical Research, Deakin University, Waurn Ponds, Victoria 3216, Australia.
Int J Mol Sci. 2018 Mar 7;19(3):766. doi: 10.3390/ijms19030766.
The ADAMTS5 metzincin, a secreted zinc-dependent metalloproteinase, modulates the extracellular matrix (ECM) during limb morphogenesis and other developmental processes. Here, the role of ADAMTS5 was investigated by knockdown of zebrafish during embryogenesis. This revealed impaired Sonic Hedgehog (Shh) signaling during somite patterning and early myogenesis. Notably, synergistic regulation of expression by ADAMTS5 and Shh during somite differentiation was observed. These roles were not dependent upon the catalytic activity of ADAMTS5. These data identify a non-enzymatic function for ADAMTS5 in regulating an important cell signaling pathway that impacts on muscle development, with implications for musculoskeletal diseases in which ADAMTS5 and Shh have been associated.
ADAMTS5 金属蛋白酶，一种分泌型锌依赖性金属蛋白酶，在肢体形态发生和其他发育过程中调节细胞外基质（ECM）。在这里，通过在胚胎发生过程中敲低斑马鱼 ，研究了 ADAMTS5 的作用。这表明 Sonic Hedgehog (Shh) 信号在体节模式形成和早期肌发生过程中受损。值得注意的是，在体节分化过程中观察到 ADAMTS5 和 Shh 对 表达的协同调节。这些作用不依赖于 ADAMTS5 的催化活性。这些数据确定了 ADAMTS5 在调节影响肌肉发育的重要细胞信号通路中的非酶功能，这与 ADAMTS5 和 Shh 相关的肌肉骨骼疾病有关。
