Role of the Peripheral Nervous System in Skeletal Development and Regeneration: Controversies and Clinical Implications

Mohamed G Hassan; Allison L Horenberg; Ariella Coler-Reilly; Warren L Grayson; Erica L Scheller

doi:10.1007/s11914-023-00815-5

Role of the Peripheral Nervous System in Skeletal Development and Regeneration: Controversies and Clinical Implications

Curr Osteoporos Rep. 2023 Oct;21(5):503-518. doi: 10.1007/s11914-023-00815-5. Epub 2023 Aug 14.

Authors

Mohamed G Hassan^#¹, Allison L Horenberg^#^{2

3}, Ariella Coler-Reilly¹, Warren L Grayson^{2

3

4

5

6}, Erica L Scheller^{7

8

9}

Affiliations

¹ Department of Medicine, Division of Bone and Mineral Diseases, Washington University, 660 South Euclid Avenue, Campus Box 8301, St. Louis, MO, 63110, USA.
² Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
³ Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD, USA.
⁴ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁵ Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁶ Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
⁷ Department of Medicine, Division of Bone and Mineral Diseases, Washington University, 660 South Euclid Avenue, Campus Box 8301, St. Louis, MO, 63110, USA. scheller@wustl.edu.
⁸ Department of Biomedical Engineering, Washington University, MO, St. Louis, USA. scheller@wustl.edu.
⁹ Department of Cell Biology and Physiology, Washington University, MO, St. Louis, USA. scheller@wustl.edu.

^# Contributed equally.

Abstract

Purpose of review: This review examines the diverse functional relationships that exist between the peripheral nervous system (PNS) and bone, including key advances over the past century that inform our efforts to translate these discoveries for skeletal repair.

Recent findings: The innervation of the bone during development, homeostasis, and regeneration is highly patterned. Consistent with this, there have been nearly 100 studies over the past century that have used denervation approaches to isolate the effects of the different branches of the PNS on the bone. Overall, a common theme of balance emerges whereby an orchestration of both local and systemic neural functions must align to promote optimal skeletal repair while limiting negative consequences such as pain. An improved understanding of the functional bidirectional pathways linking the PNS and bone has important implications for skeletal development and regeneration. Clinical advances over the next century will necessitate a rigorous identification of the mechanisms underlying these effects that is cautious not to oversimplify the in vivo condition in diverse states of health and disease.

Keywords: Bone regeneration; Denervation; Fracture healing; NGF/TrkA; Peripheral nerve; Skeletal development.

Role of the Peripheral Nervous System in Skeletal Development and Regeneration: Controversies and Clinical Implications

Authors

Affiliations

Abstract

Publication types

MeSH terms

Grants and funding