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. 2021 Feb 10;8(7):2003390. doi: 10.1002/advs.202003390

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© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Crosstalk between bone and peripheral nerves within the skeleton during heterotrophic ossification (HO). Neuropeptides and neurotransmitters from peripheral nerves regulate BAT production and mast cell degranulation. Cells derived from peripheral nerves are transported to the HO site and function as osteoprogenitors. BMP2 from the bone matrix triggers the release of neuropeptides by peripheral nerves as well as increases the permeability of blood‐nerve barrier for cells and other biological factors. NE: norepinephrine. SP: substance P. CGRP: calcitonin gene‐related peptide. BAT: brown adipose tissue. BMP2: bone morphogenetic protein 2. [Some drawing elements are adopted from SMART Servier Medical ART under the terms of the CC‐BY Creative Commons Attribution 3.0 Unported license. (http://creativecommons.org/licenses/by/3.0/).] Adapted with permission,^[ ²⁹⁹ ^] copyright 2018, Frontiers Media S.A.