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J Bone Miner Res. 2019 Aug;34(8):1393-1406. doi: 10.1002/jbmr.3822. Epub 2019 Jul 26.

Nerves in Bone: Evolving Concepts in Pain and Anabolism.

Author information

1
Department of Internal Medicine, Division of Bone and Mineral Diseases, Washington University, St. Louis, MO, USA.
2
Department of Biomedical Engineering, Washington University, St. Louis, MO, USA.
3
Department of Cell Biology and Physiology, Washington University, St. Louis, MO, USA.
4
Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.

Abstract

The innervation of bone has been described for centuries, and our understanding of its function has rapidly evolved over the past several decades to encompass roles of subtype-specific neurons in skeletal homeostasis. Current research has been largely focused on the distribution and function of specific neuronal populations within bone, as well as their cellular and molecular relationships with target cells in the bone microenvironment. This review provides a historical perspective of the field of skeletal neurobiology that highlights the diverse yet interconnected nature of nerves and skeletal health, particularly in the context of bone anabolism and pain. We explore what is known regarding the neuronal subtypes found in the skeleton, their distribution within bone compartments, and their central projection pathways. This neuroskeletal map then serves as a foundation for a comprehensive discussion of the neural control of skeletal development, homeostasis, repair, and bone pain. Active synthesis of this research recently led to the first biotherapeutic success story in the field. Specifically, the ongoing clinical trials of anti-nerve growth factor therapeutics have been optimized to titrated doses that effectively alleviate pain while maintaining bone and joint health. Continued collaborations between neuroscientists and bone biologists are needed to build on this progress, leading to a more complete understanding of neural regulation of the skeleton and development of novel therapeutics. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.

KEYWORDS:

ANALYSIS/QUANTITATION OF BONE, OTHER; BONE-BRAIN-NERVOUS SYSTEM INTERACTIONS; SYSTEMS BIOLOGY - BONE INTERACTORS, OTHER; THERAPEUTICS; THERAPEUTICS, ANABOLICS

PMID:
31247122
PMCID:
PMC6697229
[Available on 2020-08-01]
DOI:
10.1002/jbmr.3822

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