Hemiepiphysiodesis stapling induces ER stress apoptosis and autophagy in rat growth plates

半骨骺固定术诱导大鼠生长板内质网应激细胞凋亡和自噬

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作者:Jing Ding, Fangchun Jin, Xiang Zhao, Li Zhao, Zhenkai Wu, Jiyu Li

Abstract

Angular deformities of adolescents can be treated with temporary hemiepiphysiodesis. It is confirmed that mechanical staples leading to apoptosis of chondrocyte in the growth plate. In addition, clinical evidences revealed that release from growth-inhibition condition resulted in catch-up growth, which caused damage to the patients. Thus, the current study aimed to investigate the mechanisms underlying the cell growth inhibition and the rebound growth during the temporary hemiepiphysiodesis on the growth plate. Rats with knee stapling were housed for indicated weeks, then were separated into control group, hemiepiphysiodesis groups and removal of staple groups. The tissue samples were analyzed by histopathological staining or western blotting. The results indicated there was significant growth arrest and cell apoptosis in rats treated with mechanical stress loaded (hemiepiphysiodesis group). Additionally, immunohistochemistry staining and western blotting revealed the ER-stress induced cell apoptosis was involved in growth inhibition. In removal of staple group, growth-inhibition, apoptotic cells, ER stress and autophagy-related markers were all decreased when the staples were removed from mice. Moreover, IκB/NF-κB pathway were activated in the growth plate of rats when the loads were released. In conclusion, mechanical load leaded to growth inhibition in the growth plate. ER-stress induced apoptosis and autophagy might be responsible for this process. In contrast, the possible reason for the rebound growth of growth plate may be due to the elevated IκB/NF-κB activity.

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