Neuromodulation of bone: Role of different peptides and their interactions

Our understanding of the skeletal system has been expanded upon the recognition of several neural pathways that serve important roles in bone metabolism and skeletal homeostasis, as bone tissue is richly innervated. Considerable evidence provided by in vitro, animal and human studies have further elucidated the importance of a host of hormones and local factors, including neurotransmitters, in modulating bone metabolism and osteo-chondrogenic differentiation, both peripherally and centrally. Various cells of the musculoskeletal system not only express receptors for these neurotransmitters, but also influence their endogenous levels in the skeleton. As with a number of physiological systems in nature, a neuronal pathway regulating bone turnover will be neutralized by another pathway exerting an opposite effect. These neuropeptides are also critically involved in articular cartilage homeostasis and pathogenesis of degenerative joint disorders, such as osteoarthritis. In the present Review, data on the role of several neuronal populations in nerve-dependent skeletal metabolism is examined, and the molecular events involved are explored, which may reveal broader relationships between two apparently unrelated organs.