Metabolic reprogramming in osteoclasts

Osteoclasts are bone-resorbing cells that play an essential role in the remodeling of the bone. Defects in osteoclasts thus result in unbalanced bone remodeling, leading to numerous pathological conditions such as osteoporosis, bone metastasis, and inflammatory bone erosion. Metabolism is any process a cell utilizes to meet its energetic demand for biological functions. Along with signaling pathways and osteoclast-specific gene expression programs, osteoclast differentiation activates metabolic programs. The energy generated from metabolic reprogramming in osteoclasts not only supports the phenotypic changes from mononuclear precursor cells to multinuclear osteoclasts, but also facilitates bone resorption, a major function of terminally differentiated, mature osteoclasts. While oxidative phosphorylation is studied as a major metabolic pathway that fulfills the energy demands of osteoclasts, all metabolic pathways are closely interconnected. Therefore, it remains important to understand the various aspects of osteoclast metabolism, including the roles and effects of glycolysis, glutaminolysis, fatty acid synthesis, and fatty acid oxidation. Targeting the pathways associated with metabolic reprogramming has shown beneficial effects on pathological conditions. As a result, it is clear that a deeper understanding of metabolic regulation in osteoclasts will offer broader translational potential for the treatment of human bone disorders.