Chandrasekaran Kavishadhi, Hu Sitao, Farstad-O'Halloran Kara, Iyer Killugudi Swaminatha, Jiang Haibo, Pavlos Nathan, Chen Kai
School of Biomedical Sciences, University of Western Australia, Perth, WA, 6009, Australia.
School of Molecular Sciences, University of Western Australia, Perth, WA, 6009, Australia.
Curr Osteoporos Rep. 2026 Feb 9;24(1):6. doi: 10.1007/s11914-026-00955-4.
This review aims to highlight the emerging concept that nutrients and metabolites act not merely as energy sources or biosynthetic precursors, but also as instructive signalling molecules in osteoclasts. While much is known about transcriptional and genetic pathways governing osteoclast differentiation and function, comparatively little attention has been given to the role of cellular metabolism and nutrient-sensing mechanisms. This review seeks to categorise key metabolites based on their signalling roles and examine how they influence osteoclastogenesis through metabolic, epigenetic, and inflammatory pathways.
Recent studies have demonstrated that nutrients such as glucose, amino acids, and lipids, along with their intermediary metabolites such as succinate, itaconate, α-ketoglutarate (αKG), S-adenosylmethionine (SAM), and acetyl-CoA, regulate osteoclast formation and function by modulating signalling cascades and epigenetic landscapes. These molecules engage nutrient sensors (e.g., aldolase, mTORC1, CPT1) and transcriptional regulators (e.g., NFATc1, PPARs), while also affecting chromatin structure, inflammatory responses, and organelle dynamics. Osteoclast metabolism is tightly linked to cellular fate through nutrient-sensing and metabolite-driven signalling. Elucidating these pathways will reshape our understanding of osteoclast regulation and help identify new metabolic targets for treating bone diseases.
本综述旨在强调一个新出现的概念，即营养物质和代谢产物不仅作为能量来源或生物合成前体，而且在破骨细胞中作为具有指导作用的信号分子。虽然关于调控破骨细胞分化和功能的转录和遗传途径已了解很多，但对细胞代谢和营养感知机制的作用关注相对较少。本综述旨在根据关键代谢产物的信号作用进行分类，并研究它们如何通过代谢、表观遗传和炎症途径影响破骨细胞生成。
最近的研究表明，葡萄糖、氨基酸和脂质等营养物质，以及它们的中间代谢产物如琥珀酸、衣康酸、α-酮戊二酸（αKG）、S-腺苷甲硫氨酸（SAM）和乙酰辅酶A，通过调节信号级联反应和表观遗传格局来调节破骨细胞的形成和功能。这些分子与营养传感器（如醛缩酶、mTORC1、CPT1）和转录调节因子（如NFATc1、PPARs）相互作用，同时还影响染色质结构、炎症反应和细胞器动态。破骨细胞代谢通过营养感知和代谢产物驱动的信号传导与细胞命运紧密相连。阐明这些途径将重塑我们对破骨细胞调节的理解，并有助于确定治疗骨疾病的新代谢靶点。
