中药单体通过靶向自噬治疗骨质疏松症的研究进展

Chinese Medicine Monomers in Treating Osteoporosis by Targeting Autophagy:A Review

骨质疏松症是一种常见的代谢性骨疾病,其发病机制与骨内稳态的失衡密切相关。骨内稳态依赖于破骨细胞的骨吸收和间充质系成骨细胞的骨形成之间的精确动态平衡,并涉及一系列复杂且高度调节的步骤。当骨吸收速度快于骨形成时,骨内稳态将被破坏,进而导致骨质疏松。自噬是蛋白质和细胞器降解和循环的基本途径之一,是调节细胞和有机体稳态的基础过程。重要的是,自噬的基本水平存在于所有3种类型的骨相关细胞中。由于自噬的循环特性及持续的骨重塑过程,自噬被认为是骨骼维护的新参与者。新机制的出现带来了新的治疗靶点,通过靶向自噬中的特定调节分子来干预自噬可以调节骨代谢过程。同时,随着中医药在骨质疏松症治疗领域中的研究逐渐深入,人们发现从传统中草药中分离出的中药单体表现出良好的调节自噬治疗骨质疏松症的潜力。基于此,该文讨论了自噬与骨质疏松症的相互关系,并根据最新相关研究进展,总结出22种中药单体通过靶向自噬治疗骨质疏松症的6项不同作用机制,包括靶向自噬增加骨髓间充质干细胞的成骨分化、促进成骨细胞矿化,抑制破骨细胞分化、减少骨相关细胞凋亡、拮抗氧化应激损伤和协调炎症与自噬水平,以期为今后更多中药单体治疗骨质疏松症的有关研究提供参考和思路。

Osteoporosis,a common metabolic bone disease,is caused by the imbalance of bone homeostasis. Bone homeostasis depends on the dynamic balance between bone resorption by osteoclasts and bone matrix formation by mesenchymal lineage osteoblasts and involves a series of complex and highly regulated steps. When bone resorption is faster than bone formation,bone homeostasis will be destroyed,which will lead to osteoporosis. Autophagy is a protein and organelle degradation pathway important for the maintenance of cytoplasmic homeostasis. The basal level of autophagy is present in all the three types of bone cells. Autophagy is a process whereby damaged organelles are recycled and bone remodeling continues,and thus it plays an important role in bone maintenance. Therefore,it is possible to regulate bone metabolism by targeting specific autophagy-related molecules. At the same time,as the research on the treatment of osteoporosis by Chinese medicine advances,it is found that the monomers isolated from traditional Chinese medicinals have the potential of regulating autophagy in the treatment of osteoporosis. Thus,this paper discusses the relationship between autophagy and osteoporosis and summarizes six different mechanisms of 22 Chinese medicine monomers in the treatment of osteoporosis through targeting autophagy:increasing osteogenic differentiation of mesenchymal stem cells,promoting osteoblast mineralization,inhibiting osteoclasts differentiation,reducing apoptosis of bone cells,antagonizing oxidative stress injury,and coordinating inflammation and autophagy levels. The review is expected to provide a reference and ideas for future research on the treatment of osteoporosis by Chinese medicine monomers.