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. 2021 Oct 26;6:70. doi: 10.1038/s41536-021-00178-4

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — Mononuclear macrophages are polarized to the M1-M2 macrophages in injured tissues in responding to injury. Macrophages secrete OSM and TGF-β1, BMPs, Act A, SP, and VEGF, and promote the expression of NT-3 and other factors. These signal molecules through different signal pathways, including TGF-β1-Smad2/3 and BMP-Smad1/5/8, jointly induce osteogenesis of MSCs, angiogenesis, and proper microenvironment formation, promoting the occurrence and development of HO through multiple pathways.