脂代谢与骨代谢信号通路及与骨代谢相关疾病的关系:理论进展与热点方向

Correlation of the signaling pathways of bone metabolism and lipid metabolism with bone metabolism related diseases: theoretical advance and research direction

背景:近年来以肥胖、高血脂及高血糖为主要表现的代谢综合征也越来越高发,同时脂代谢的异常可带来骨代谢的异常,脂代谢的紊乱会导致骨质疏松、骨质流失和骨关节炎等骨代谢相关疾病的发生。目的:总结脂代谢与骨代谢之间的主要通路,探究脂代谢与骨代谢相关疾病之间的关联,以期找到脂代谢作用于骨代谢疾病的具体靶点。方法:应用计算机检索Pub Med数据库及CNKI数据库的相关文章,检索时间为2000年1月至2017年7月,以"脂代谢,骨代谢,骨髓间充质干细胞,骨质疏松,骨关节炎"为中文检索词,以"bone metabolism,lipid metabolism,bone marrow mesenchymal stem cells,osteoarthritis,osteoporosis"为英文检索词。初步检索156篇文献,阅读标题和摘要,排除与主题不相关的文献,最后纳入58篇文献进行结果分析。结果与结论:(1)脂代谢和骨代谢主要通过Wnt/β-catenin、过氧化物酶体增殖物激活受体γ、瘦素、骨形态发生蛋白、固醇调节元件结合蛋白和氧化应激等信号通路协同作用和相互制约;(2)脂代谢可以通过这些通路来影响骨代谢相关疾病,包括骨质疏松、骨关节炎、骨质软化等;(3)他汀类药物可以通过激活Wnt通路和抑制过氧化物酶体增殖物激活受体γ通路,起到治疗脂代谢异常带来的骨质疏松和骨质流失的作用;(4)未来,可以进一步着眼于脂代谢影响骨代谢疾病的具体通路机制,以期能够寻找到脂代谢作用于骨代谢疾病的具体靶点,达到治疗骨代谢疾病的目的。

BACKGROUND： Recently, the incidence of metabolic syndrome characterized by obesity, hyperlipidemia, and hyperglycemia is on a rise. Lipid metabolism disorder can lead to bone metabolism disorder, further inducing osteoporosis, bone loss, and osteoarthritis. OBJECTIVE： To summarize the main pathways between bone metabolism and lipid metabolism, explore the relationship between lipid metabolism and bone metabolism related disease, and provide new therapeutic direction for bone metabolism related diseases. METHODS： A computer-based search for literature in Pub Med and CNKI databases published from January 2000 to July 2017 was performed using the keywords of ＂bone metabolism, lipid metabolism, bone marrow mesenchymal stem cells, osteoarthritis, osteoporosis＂ in English and Chinese, respectively. A total of 156 articles were retrieved and 58 eligible articles were in accordance with the inclusion and exclusion criteria after reading the title and abstract.RESULTS AND CONCLUSIONS： Lipid metabolism interacts with bone metabolism mainly by Wnt/β-catenin, PPARγ, leptin, bone morphogenetic protein, SREBP and oxidative stress pathways. Lipid metabolism can affect bone metabolism related diseases, including osteoporosis, osteoarthritis, and bone softening. Statins can treat osteoporosis and bone loss induced by lipid metabolism disorders through activation of Wnt pathway and inhibition of PPARγ pathway. In the future, we devote ourselves to finding the special target at which lipid metabolism is conducive to treatment of bone metabolic diseases.