线粒体自噬调控骨代谢

Mitophagy regulates bone metabolism

背景:近年来大量的研究表明,自噬和线粒体自噬在骨代谢过程中扮演着重要角色,非生理状态下的线粒体自噬会打破骨代谢的平衡导致代谢紊乱,对成骨细胞、破骨细胞、骨细胞、软骨细胞、骨髓间充质干细胞等均可产生影响。目的:归纳线粒体自噬调节骨代谢疾病的作用机制及在临床治疗领域的应用。方法:应用计算机检索PubMed、Web of Science、中国知网、万方和维普等数据库,中文关键词为“线粒体自噬,骨代谢,成骨细胞,破骨细胞,骨细胞,软骨细胞,骨髓间充质干细胞”,英文关键词为“mitophagy,bone metabolism,osteoblast,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells”,检索文献时限为2008-2023年。依据入选标准对检索结果进行筛选排除,最终纳入90篇文献进行综述分析。结果与结论:线粒体自噬通过SIRT1、PINK1/Parkin、FOXO3、PI3K信号通路促进成骨细胞生成,通过PINK1/帕金森相关蛋白和SIRT1信号通路抑制破骨细胞功能,通过增加骨质中的磷酸钙颗粒和组织蛋白激酶K导致骨质流失,通过PINK1/帕金森相关蛋白、PI3K/AKT/mTOR、AMPK信号通路提高软骨细胞功能。尽管调控线粒体自噬在治疗骨病方面显示出巨大潜力,但仍有一些问题有待进一步探究,例如:药物激活线粒体自噬的不同阶段、不同信号通路的调控机制等。

BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc.OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment.METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of“mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells”in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis.RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.