Excess muscle plasma membrane leak disrupts ECM content and shifts macrophage-mediated muscle repair.

Cell metabolism underpins the normal physiological functions of cells. All tissues and organs in the body derive their energy through cellular metabolic processes, during which substantial amounts of fats and proteins are consumed. Multiple mechanisms of energy and substrate metabolism have been identified, among which the direct consumption of glucose and fatty acids is most common. In animal experiments, glucose or its aqueous solution is often introduced into the cell culture medium to stimulate osteoblasts. In human studies, biological materials such as cholesterol, triglycerides, phospholipids, and sphingolipids are frequently used to stimulate osteoblasts. Additionally, adipose tissue has been shown to promote osteogenesis by stimulating the synthesis and secretion of bone matrix components and by directly consuming amino acids. Beyond the direct consumption of energy and substrates, cellular metabolism also affects bone formation and maintenance through influences on mitochondrial function, ribosomal function, and the expression of various proteins. Osteoblasts and osteoclasts are the primary representative bone cells. This review summarizes key studies on osteoblasts and osteoclasts, along with the associated metabolic pathways and mechanisms, from the perspective of cell metabolism. The authors also discuss the classifications of cellular metabolism relevant to bone and cartilage regeneration, bone homeostasis, and metabolic bone diseases. Despite established roles of glycolysis, oxidative phosphorylation, and Wnt/NF-κB in osteoblast metabolism, fundamental gaps persist. For instance, metabolic heterogeneity among osteoblast subtypes (e.g., matrix-synthesizing vs. mineralizing osteoblasts) remains uncharacterized, and its implications for bone diseases like osteoporosis are unexplored. Further, conflicting evidence on mTORC1’s dual anabolic/catabolic roles in bone formation warrants systematic reevaluation. The work adheres to the PRISMA guidelines, and no new human or animal research was conducted.