ADPN

Adiponectin, a key adipokine with metabolic and anti-inflammatory properties, plays a crucial role in multiple organs, including the cardiovascular system, muscle, liver, adipose tissue, brain, and bone. Recent studies have explored adiponectin signaling in bone metabolism, but human association studies and mouse models have yet to establish a clear cause-and-effect relationship. This complexity may stem from the different multimeric forms of adiponectin, which exhibit variable receptor binding (AdipoR1 and AdipoR2) depending on cell-specific receptor variants in bone. The discovery of small-molecule AdipoR1 agonists suggests a potential regulatory role of this receptor in bone metabolism. AdipoR1 activation in osteoblasts promotes oxidative phosphorylation, enhancing differentiation likely via suppression of the Wnt inhibitor sclerostin. Additionally, adiponectin’s anti-inflammatory signaling reduces the RANKL-to-OPG ratio in osteoblasts, thereby inhibiting osteoclastogenesis. This review evaluates the role of adiponectin signaling in skeletal homeostasis and explores the therapeutic potential of AdipoR1 as a target for metabolic bone disorders.