内质网应激与骨细胞及相关骨病的研究进展

Research progress in endoplasmic reticulum stress and osteocytes and the relevant bone diseases

内质网(endoplasmic reticulum,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时,内质网应激(endoplasmic reticulum stress,ERS)启动,并引发未折叠蛋白反应、内质网超负荷反应和固醇调节级联反应。在应激状态下,ER对维持细胞内稳态起到至关重要的作用。一方面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。另一方面在高强度长时间应激状态下,ERS无法维持细胞稳态,会通过多种信号通路诱导细胞凋亡的发生,加速细胞更新。根据近几年已有报道的文献研究整理,在骨质疏松、成骨不全、氟骨症等相关骨病的研究中,ERS同样发挥着重要的调节作用。特别是在发病早期,ERS通过对多种骨细胞的调节,缓解病情。当病情严重ERS会触发内质网凋亡信号,导致细胞凋亡和生物体的损伤。本文就近年来国内外对ERS与骨细胞及相关骨病的研究进展进行综述。

Endoplasmic reticulum （ER） is an important intracellular membrane structure. It is responsible for folding process of the secreted protein and membrane protein, the biosynthesis of lipids, and calcium balance. When the endoplasmic reticulum environmental changes, such as ischemia, hypoxia, an substantial accumulation of misfolded proteins, ER stress is activated, accompanying with unfolded protein response （UPR）, the endoplasmic reticulum overload （EOR） and cholesterol regulation cascade reaction. Under stress, ER plays an important role in cellular homeostasis. On the one hand, ER stress promotes the growth of osteoblasts, osteoclasts, chondrocytes, and the differentiation of osteoblasts from mesenchymal stem cells and restrain apoptosis. On the other hand, ER stress loses the control of cellular homeostasis and induces apoptosis to accelerate cell turnover when the stress is strong and continuous. According to the literature reported in recent years, ER stress plays a vital modulator role in a variety of bone diseases, including osteoporosis, osteogenesis, imperfect, and skeletal fluorosis. Especially during the early stage of these diseases, ER stress alleviates the patients＇ condition by regulating osteocytes. Apoptosis can be activated by long-term ER stress, which can result in cell apoptosis and damage on organism. In this review, we summarize the relationship between ER stress and bone diseases and the related cells.