Mechano-growth factor protects against mechanical overload induced damage and promotes migration of growth plate chondrocytes through RhoA/YAP pathway

Experimental Cell Research
Xingzhi JingFengjing Guo

Abstract

Epiphyseal growth plate is highly dynamic tissue which is controlled by a variety of endocrine, paracrine hormones, and by complex local signaling loops and mechanical loading. Mechano growth factor (MGF), the splice variant of the IGF-I gene, has been discovered to play important roles in tissue growth and repair. However, the effect of MGF on the growth plate remains unclear. In the present study, we found that MGF mRNA expression of growth plate chondrocytes was upregulated in response to mechanical stimuli. Treatment of MGF had no effect on growth plate chondrocytes proliferation and differentiation. But it could inhibit growth plate chondrocytes apoptosis and inflammation under mechanical overload. Moreover, both wound healing and transwell assay indicated that MGF could significantly enhance growth plate chondrocytes migration which was accompanied with YAP activation and nucleus translocation. Knockdown of YAP with YAP siRNA suppressed migration induced by MGF, indicating the essential role of YAP in MGF promoting growth plate chondrocytes migration. Furthermore, MGF promoted YAP activation through RhoA GTPase mediated cytoskeleton reorganization, RhoA inhibition using C3 toxin abrogated MGF induced YAP activation. Impor...Continue Reading

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