Defective autophagy in osteoblasts induces endoplasmic reticulum stress and causes remarkable bone loss

	Defective autophagy in osteoblasts induces endoplasmic reticulum stress and causes remarkable bone loss
	Li, Danhui; Li, Huixia; Ma, Zhengmin; Qian, Zhuang; Kang, Xiaomin; Jin, Xinxin; Li, Fang; Wang, Xinluan; Chen, Qian; Sun, Hongzhi
刊名	AUTOPHAGY
	2018
文献子类	期刊论文
英文摘要	Macroautophagy/autophagy is a highly regulated process involved in the turnover of cytosolic components, however its pivotal role in maintenance of bone homeostasis remains elusive. In the present study, we investigated the direct role of ATG7 (autophagy related 7) during developmental and remodeling stages in vivo using osteoblast-specific Atg 7 conditional knockout (ckO) mice. Atg7 cKO mice exhibited a reduced bone mass at both developmental and adult age. The trabecular bone volume of Atg7 ckO mice was significantly lower than that of controls at 5 months of age. Thisphenotype was attributed to decreased osteoblast formation and matrix mineralization, accompanied with an increased osteoclast number and the extent of the bone surface covered by osteoclasts as well as an elevated secretion of TNFSF11/RANKL (tumor necrosis factor [ ligand] superfamily, member 11), and a decrease in TNFRSF11B/OPG(tumor necrosis factor receptor superfamily, member 11b [ osteoprotegerin]). Remarkably, Atg7 deficiency in osteoblasts triggered endoplasmic reticulum (ER) stress, whereas attenuation of ER stress by administration of phenylbutyric acid in vivo abrogated Atg7 ablation-mediated effects on osteoblast differentiation, mineralization capacity and bone formation. Consistently, Atg7 deficiency impeded osteoblast mineralization and promoted apoptosis partially in DDIT3/CHOP(DNA-damage-inducible transcript 3)-and MAPK8/JNK1(mitogen-activated protein kinase 8-SMAD1/5/8-dependent manner in vitro, while reconstitution of Atg7 could improveER stress and restore skeletal balance. In conclusion, our findings provide direct evidences thatautophagy plays crucial roles in regulation of bone homeostasis and suggest an innovative therapeutic strategy against skeletal diseases.
URL标识	查看原文
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/14429]
专题	深圳先进技术研究院_医工所
推荐引用方式 GB/T 7714	Li, Danhui,Li, Huixia,Ma, Zhengmin,et al. Defective autophagy in osteoblasts induces endoplasmic reticulum stress and causes remarkable bone loss[J]. AUTOPHAGY,2018.
APA	Li, Danhui.,Li, Huixia.,Ma, Zhengmin.,Qian, Zhuang.,Kang, Xiaomin.,...&Wu, Shufang.(2018).Defective autophagy in osteoblasts induces endoplasmic reticulum stress and causes remarkable bone loss.AUTOPHAGY.
MLA	Li, Danhui,et al."Defective autophagy in osteoblasts induces endoplasmic reticulum stress and causes remarkable bone loss".AUTOPHAGY (2018).