Fig. 4

Sympathetic neurotransmitter-mediated regulatory mechanisms in bone-related diseases. This schematic delineates the role of sympathetic nervous system (SNS) signaling in osteoporosis, osteoarthritis (OA), rheumatoid arthritis (RA), and intervertebral disc degeneration (IVDD). Osteoporosis: Norepinephrine (NE) activates β-adrenergic receptors (β-ARs), suppressing osteoblast (OB) differentiation and promoting osteoclast (OC) activity. Leptin exacerbates bone loss via the hypothalamus-SNS-bone axis, decreasing the osteoprotegerin (OPG)/RANKL ratio. OA: β2-AR signaling inhibits chondrocyte proliferation and induces apoptosis, accelerating cartilage degeneration. Dopamine (DA) alleviates inflammation through anti-inflammatory pathways. Neuropeptide Y (NPY) and leptin activate the mechanistic target of rapamycin complex 1 (mTORC1), driving chondrocyte senescence. RA: Early phase: The SNS hyperactivity aggravates synovitis via NE-mediated pathways. Late phase: NE signaling reduces inflammation. DA suppresses IL-6 and IL-8 secretion in rheumatoid arthritis synovial fibroblasts (RASFs), mitigating inflammation. IVDD: β-AR activation disrupts extracellular matrix (ECM) homeostasis, promoting disc degeneration. NPY inhibits the NF-κB pathway, attenuating nucleus pulposus cell (NPC) apoptosis. Symbols: ↑ activation or increase; ↓ inhibition or decrease; and (−) suppression