Fig. 2

Molecular mechanisms of the sympathetic neurotransmitter-mediated regulation of osteoblast (OB) and osteoclast (OC) homeostasis. This schematic delineates the signaling pathways by which norepinephrine (NE), dopamine (DA), and neuropeptide Y (NPY) modulate bone remodeling through their respective receptors: β-adrenergic receptors (β-ARs), dopamine receptors D1R/D2R, and neuropeptide Y receptor Y1R. The key regulatory modules include the following: (1) NE/β-AR pathway: NE activates β-ARs, triggering the cAMP/PKA/CREB cascade, which suppresses osteoblast differentiation (by downregulating RUNX family transcription factor 2, RUNX2↓) and enhances osteoclast activity (by upregulating the receptor activator of nuclear factor kappa-B ligand, RANKL↑). (2) DA/D1R-D2R pathway: DA exerts bidirectional effects on bone metabolism: D1R activation promotes osteogenesis, while D2R signaling inhibits osteoclastogenesis, demonstrating receptor subtype-specific regulation. (3) NPY/Y1R pathway: NPY binding to Y1R inhibits the osteogenic differentiation of mesenchymal stem cells (MSCs), diverting their fate toward the adipocyte lineage (adipogenesis↑), thereby disrupting bone formation. Symbols: → activation; ⊣ inhibition