Ding Jing, Jin Fangchun, Zhao Xiang, Zhao Li, Wu Zhenkai, Li Jiyu
Department of Pediatric Orthopaedics, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200092, China.
Department of Pediatric Orthopaedics, Ying-Hua Medical Group of Children's Bone and Joint Healthcare Shanghai 200000, China.
Am J Transl Res. 2019 Mar 15;11(3):1486-1497. eCollection 2019.
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.
青少年的角状畸形可通过临时半骺阻滞术进行治疗。已证实机械吻合钉可导致生长板中的软骨细胞凋亡。此外，临床证据表明，从生长抑制状态释放会导致追赶生长，这对患者造成损害。因此，本研究旨在探讨临时半骺阻滞术期间生长板细胞生长抑制和反弹生长的潜在机制。将行膝关节吻合钉固定的大鼠饲养指定周数，然后分为对照组、半骺阻滞组和拆除吻合钉组。通过组织病理学染色或蛋白质印迹法分析组织样本。结果表明，机械应力加载处理的大鼠（半骺阻滞组）出现了显著的生长停滞和细胞凋亡。此外，免疫组织化学染色和蛋白质印迹法显示内质网应激诱导的细胞凋亡参与了生长抑制。在拆除吻合钉组中，从小鼠体内取出吻合钉后，生长抑制、凋亡细胞、内质网应激和自噬相关标志物均减少。此外，当负荷解除时，大鼠生长板中的IκB/NF-κB通路被激活。总之，机械负荷导致生长板生长抑制。内质网应激诱导的凋亡和自噬可能是这一过程的原因。相反，生长板反弹生长的可能原因可能是IκB/NF-κB活性升高。
