自噬在生长板软骨细胞中通过调控colII分泌参与软骨分化，是骨生长必需的发育调节过程。我们前期研究表明(81171697)：IRE1作为ER stress核心通路分子，与BMP2/PGRN形成负反馈环调控骨形成；IRE1软骨特异性敲除(IRE1-/- cKO)小鼠生长板软骨细胞中，自噬标志基因ATG5/LC3β表达显著降低，自噬不能激活，提示IRE1可能通过自噬调控生长板软骨发育，具体机制不清楚。本研究综合运用IRE1-/-cKO小鼠和对照小鼠，结合三种不同类型干细胞微团培养、小鼠软骨细胞原代培养、体外趾骨组织团块培养、IHC、Q-PCR、免疫印迹等方法，检测IRE1对三种不同类型自噬的调控作用；分析IRE1如何通过自噬调控软骨发育；阐明IRE1调节软骨细胞分化是否依赖于自噬及下游JNK/NF-κB/P38/Erk1/2等信号通路；揭示IRE1调节的细胞自噬在生长板软骨发育中的作用与机制。

Autophagy participates in the development of growth plate cartilage with the secretion of type II collagen(Col2), which is the necessary developmental regulation process. Our previous study(81171697) showed that IRE1,with BMP2/PGRN, forms a negative feedback loop and acts in concert in the course of osteoblastogenesis as a core molecule of ER stress.The expression of autophagy associated gene ATG5/LC3β reduced remarkably in the IRE1 conditional knockout mice, and autophagy can not be activated.It is showed that IRE1 can regulate the.development of growth plate cartilage through cell autophagy,however,the mechanism also remains unknown. In this study,we integrated use the IRE1 conditional knockout (cKO) mice and wild type mice, combined with such methods as stem cell micromass culture, mouse chondrocyte primary culture, mouse metatarsal bones induced culture in vitro, immunohistochemistry(IHC), Q-PCR and immunoblotting, detected the regulation of IRE1 on three types autophagy, analyzed on how to regulate cartilage development through autophagy, clarified whether IRE1 regulated chondrocyte development depends on autophagy and the downstream JNK/NF-κB/P38/Erk1/2 signal pathway, revealed the effect and mechanism of IRE1-modulated autophagy in the development of growth plate cartilage.