From nerve to bone: a tale of autonomic nervous system, bone cells, and beyond.

Bone is a multifunctional organ essential for structural support, protection, hematopoiesis, and endocrine regulation. Emerging research increasingly highlights the pivotal role of the nervous system in bone metabolism, repair, and musculoskeletal disease progression, particularly the autonomic nervous system (ANS), which precisely regulates bone tissue cells via sympathetic and parasympathetic pathways. The ANS regulates the activity of mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, chondrocytes, and nucleus pulposus cells (NPCs) via neurotransmitters such as norepinephrine (NE), acetylcholine (ACh), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP), thereby modulating core pathological processes in bone-related disorders including osteoporosis (OP), osteoarthritis (OA), intervertebral disc degeneration (IVDD), and traumatic fractures. Targeted neuromodulation is emerging as a promising therapeutic strategy for musculoskeletal disorders. This review aims to summarize the regulatory roles of the ANS in bone cell metabolism and bone-related pathologies and to evaluate current ANS-bone axis-based interventions to promote skeletal health and alleviate the burden of musculoskeletal diseases.