新型气体信号分子H_2S与骨代谢的研究概况

New gaseous signal molecule H_2S and bone metabolism

硫化氢被证明为第三种内源性气体信号分子,并被发现有许多新型的功能,通过不断研究发现硫化氢与骨代谢有密切关系,并对硫化氢对骨代谢的影响及机制逐步研究。在体外细胞研究发现成骨细胞表达CSE增强ALP活性、成骨分化,H_2S可促进RANKL诱导的破骨细胞分化,抑制破骨细胞的增殖,减弱破骨作用;但其他观点H_2S可增加细胞内抗氧化剂谷胱甘肽,进而增强破骨细胞的分化,观点有争议。动物模型研究发现H_2S可以治疗雌激素缺乏引起的骨量丢失;高浓度的H_2S可加重类风湿性关节炎大鼠的炎症反应,而低浓度的H_2S可以减轻炎症反应。人体方面研究发现多种疾病如股骨头脱臼,骨质疏松症与CBS缺乏症相关,骨折血浆中H_2S含量明显降低,H_2S在骨折愈合过程中降低局部炎性细胞浸润并抑制成骨细胞中的氧化应激反应,对成骨细胞起到保护作用。前期研究以体外研究为主,对人体直接相关研究甚少;以及体内是否存在内源性H_2S及如何改变内源性H_2S需要进一步研究,通过总结分析,多位学者的结论存在争议,所以我们对有关文献进行梳理,以期为揭示硫化氢与骨代谢及调控骨质疏松机制的研究提供新的思路。

H2S has been proved to be the third endogenous signal molecule and was found to have many newfeatures. Many researchers found that there are close relationships between H2S and bone metabolism,and have studied the influence of H2S on bone metabolism and the relevant mechanism. In in vitro studies,researchers proved that osteoblasts express CSE and increase the activity of ALP and differentiation. H2S promotes RANKL-induced osteoclast differentiation; inhibit the proliferation of osteoclasts and decrease bone resorption,but there are other opinions. In animal model studies,H2S can prevent estrogen deficiency induced bone loss; high concentrations of H2S can aggravate the inflammation of rheumatoid arthritis in rats,while lowconcentrations can reduce inflammation. Studies found a variety of human diseases such as femoral head dislocation and osteoporosis associated with CBS deficiency. H2S can decrease inflammation and inhibit oxidative stress during fracture healing and protect osteoblasts. Previous studies were mainly in vitro not in vivo; and further study should be conducted to confirm if H2S exist in vivo. In summary of findings of previous research,we found that there are different opinions. So we reviewed the relevant papers,with the aim to provide newideas on the regulation of bone metabolism and osteoporosis by H2S and the relevant mechanisms.