内质网应激相关基因调控骨生长发育的研究进展

Advances in studies on bone growth and development of stress-related genes in endoplasmic reticulum

内质网(ER)作为细胞内重要的膜性结构,负责分泌蛋白与膜蛋白的折叠加工、脂类的生物合成以及钙平衡的调节。当ER环境发生改变,如缺血、缺氧、突变蛋白的大量堆积,内质网应激(ERS)启动,并引发未折叠蛋白反应(UPR)、内质网超负荷反应和类固醇调节级联反应。ERS与很多因素所致疾病的发生、发展密切相关,常见有神经系统变性疾病、糖尿病、病毒感染性疾病以及一些化学毒物中毒引起的疾病。在骨生长发育方面,ERS有助于成骨细胞、破骨细胞和软骨细胞的生长,可以促进骨髓间充质干细胞向成骨细胞的分化,并抑制细胞凋亡的发生,同时ERS传感器基因的异常与骨质疏松、成骨不全、氟骨症等相关骨病的发生密切相关。笔者就ERS相关基因调控骨生长发育做一综述。

Endoplasmic reticulum （ER）, as an important intracellular membrane structure, is responsible for the folding of protein and membrane proteins, the biosynthesis of lipids and the regulation of calcium balance. When the ER environment changed, such as ischemia, hypoxia, massive accumulation of mutant proteins, endoplasmic reticulum stress （ERS） starts, triggering unfolded protein reactions（UPR）, endoplasmic reticulum overload and sterol regulatory cascade reaction. ERS is closely related to the occurrence and development of many diseases, such as nervous system degeneration, diabetes and viral infectious diseases and some diseases caused by some chemical poisonings. ERS contributes to the growth of osteoblasts, osteoclasts and chondrocytes in bone growth and development, which can promote the differentiation of bone marrow mesenchymal stem cells into osteoblasts and inhibit the occurrence of cell apoptosis. At the same time,the abnormality of ERS sensor genes are closely related to the occurrence of osteoporosis, osteogenesis imperfecta, fluorosis of bone and other related bone diseases. This article reviews the regulation of ERS related genes in the growth and development of bone.