Abstract
Bone is a dynamic tissue and is constantly being remodeled by bone cells. Metabolic reprogramming plays a critical role in the activation of these bone cells and skeletal metabolism, which fulfills the energy demand for bone remodeling. Among various metabolic pathways, the importance of lipid metabolism in bone cells has long been appreciated. More recent studies also establish the link between bone loss and lipid-altering conditions—such as atherosclerotic vascular disease, hyperlipidemia, and obesity—and uncover the detrimental effect of fat accumulation on skeletal homeostasis and increased risk of fracture. Targeting lipid metabolism with statin, a lipid-lowering drug, has been shown to improve bone density and quality in metabolic bone diseases. However, the molecular mechanisms of lipid-mediated regulation in osteoclasts are not completely understood. Thus, a better understanding of lipid metabolism in osteoclasts can be used to harness bone cell activity to treat pathological bone disorders. This review summarizes the recent developments of the contribution of lipid metabolism to the function and phenotype of osteoclasts.
Highlights
The skeleton is a dynamic tissue that undergoes constant remodeling by bone resorbing osteoclasts and bone forming osteoblasts [1,2]
Packages of verylow-density lipoproteins (VLDLs) with TGs and cholesterol are synthesized in the liver and hydrolyzed in muscle and adipose tissue by lipoprotein lipase (LPL) and VLDL remnants; free fatty acids are released for cellular uptake
This study showed that impaired osteoclastogenesis in low density lipoprotein (LDL) receptors (LDLR)-deficient osteoclasts was rescued by the addition of cholesterol [45], suggesting that LDLR-mediated cholesterol uptake by macrophage might be required for osteoclastogenesis
Summary
The skeleton is a dynamic tissue that undergoes constant remodeling by bone resorbing osteoclasts and bone forming osteoblasts [1,2]. Bone-embedded osteocytes, derived from terminally differentiated osteoblasts, coordinate bone remodeling by detecting damage and sending a signal to osteoclasts and osteoblasts [9]. Bone remodeling is notably sensitive to environmental changes, including metabolic perturbation. Lipids in bone and bone marrow fuel this process and play an essential role in controlling the differentiation and function of bone cells [10]. Excessive lipid accumulation is directly correlated with changes in bone mass. Fat accumulation is inversely correlated with bone quality in obese humans, and high-fat-diet-fed mice show excess adiposity, low bone mineral density (BMD), and compromised bone quality [11]. The role and function of lipid metabolism in osteoclasts have not been well understood. This review summarizes the recent findings for the role of lipid metabolism in osteoclasts and discusses the effect of the regulation of lipid metabolism on osteoclasts and on the skeleton
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