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J Cell Physiol. 2019 May;234(5):5466-5477. doi: 10.1002/jcp.26502. Epub 2018 Dec 7.

Neural regulation of bone remodeling: Identifying novel neural molecules and pathways between brain and bone.

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Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
The Brain Cognition & Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Department of Nephrology, Shenzhen People's Hospital, Second Clinical Medical College, Jinan University, Shenzhen, China.
Program in Biological Sciences in Dental Medicine, Harvard School of Dental Medicine, Boston, Massachusetts.


The metabolism and homeostasis of the skeletal system have historically been considered to be associated with the endocrine system. However, this view has been expanded with the recognition of several neural pathways playing important roles in the regulation of bone metabolism via central relays. In particular, bone metabolism and homeostasis have been reported to be precisely modulated by the central neural signaling. Initiated by the finding of leptin, the axis of neural regulation on bone expands rapidly. The semaphorin-plexin system plays an important role in the cross-talk between osteoclasts and osteoblasts; a complex system has also been identified and includes neuropeptide Y and cannabinoids. These findings facilitate our understanding of the central neuropeptides and neural factors in the modulation of bone metabolism and homeostasis, and these neuronal pathways also represent an area of research scenario that identifies the novel regulation between brain and bone. These regulatory mechanisms correlate with other homeostatic networks and demonstrate a more intricate and synergetic bone biology than previously envisioned. As such, this review summarizes the current knowledge of the neural regulation of bone metabolism and homeostasis, as well as its role in skeletal diseases and discusses the emerging challenges presented in this field.


bone; leptin; neural regulation; neuropeptide Y; semaphorin


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