College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, People's Republic of China.
Center of Excellence for Vector-Borne Diseases, Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, 66502, USA.
Biol Cell. 2020 Sep;112(9):251-264. doi: 10.1111/boc.202000008. Epub 2020 Jun 8.
Osteoclasts are multinucleated giant cells, responsible for bone resorption. Osteoclast differentiation and function requires a series of cytokines to remove the old bone, which coordinates with the induction of bone remodelling by osteoblast-mediated bone formation. Studies have demonstrated that AMP-activated protein kinase (AMPK) play a negative regulatory role in osteoclast differentiation and function. Research involving AMPK, a nutrient and energy sensor, has primarily focused on osteoclast differentiation and function; thus, its role in autophagy, inflammation and immunity remains poorly understood. Autophagy is a conservative homoeostatic mechanism of eukaryotic cells, and response to osteoclast differentiation and function; however, how it interacts with inflammation remains unclear. Additionally, based on the regulatory function of different AMPK subunits for osteoclast differentiation and function, its activation is regulated by upstream factors to perform bone metabolism. This review summarises the critical role of AMPK-mediated autophagy, inflammation and immunity by upstream and downstream signalling during receptor activator of nuclear factor kappa-B ligand-induced osteoclast differentiation and function. This pathway may provide therapeutic targets for bone-related diseases, as well as function as a biomarker for bone homoeostasis.
破骨细胞是多核巨细胞，负责骨吸收。破骨细胞的分化和功能需要一系列细胞因子来去除旧骨，这与成骨细胞介导的骨形成所诱导的骨重建相协调。研究表明，腺苷酸活化蛋白激酶（AMPK）在破骨细胞的分化和功能中起负调控作用。涉及作为营养和能量传感器的 AMPK 的研究主要集中在破骨细胞的分化和功能上；因此，其在自噬、炎症和免疫中的作用仍知之甚少。自噬是真核细胞的一种保守的同源平衡机制，对破骨细胞的分化和功能有反应；然而，它与炎症如何相互作用尚不清楚。此外，基于不同 AMPK 亚基对破骨细胞分化和功能的调节作用，其激活受上游因子的调节，以进行骨代谢。本综述总结了在核因子 κB 配体诱导的破骨细胞分化和功能过程中，上游和下游信号通过 AMPK 介导线粒体自噬、炎症和免疫的关键作用。该途径可为骨相关疾病提供治疗靶点，并作为骨稳态的生物标志物。
