The human skeleton is a multifunctional organ made up of multiple cell types working in concert to maintain bone and mineral homeostasis and to perform critical mechanical and endocrine functions. From the beginning steps of chondrogenesis that prefigures most of the skeleton, to the rapid bone accrual during skeletal growth, followed by bone remodeling of the mature skeleton, cell differentiation is integral to skeletal health. While growth factors and nuclear proteins that influence skeletal cell differentiation have been extensively studied, the role of cellular metabolism is just beginning to be uncovered. Besides energy production, metabolic pathways have been shown to exert epigenetic regulation via key metabolites to influence cell fate in both cancerous and normal tissues. In this review, we will assess the role of growth factors and transcription factors in reprogramming cellular metabolism to meet the energetic and biosynthetic needs of chondrocytes, osteoblasts, or osteoclasts. We will also summarize the emerging evidence linking metabolic changes to epigenetic modifications during skeletal cell differentiation.

人体骨骼是一个由多种细胞类型组成的多功能器官，它们协同工作以维持骨骼和矿物质稳态，并执行关键的机械和内分泌功能。从预示大部分骨骼的软骨形成的开始步骤，到骨骼生长过程中的快速骨骼积累，再到成熟骨骼的骨骼重塑，细胞分化是骨骼健康不可或缺的一部分。虽然影响骨骼细胞分化的生长因子和核蛋白已被广泛研究，但细胞代谢的作用才刚刚开始被揭示。除了能量产生外，代谢途径还通过关键代谢物发挥表观遗传调控作用，以影响癌组织和正常组织中的细胞命运。在这篇综述中，我们将评估生长因子和转录因子在重编程细胞代谢中的作用，以满足软骨细胞、成骨细胞或破骨细胞的能量和生物合成需求。我们还将总结骨骼细胞分化过程中将代谢变化与表观遗传修饰联系起来的新证据。