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. 2021 Sep 21;9:714011. doi: 10.3389/fcell.2021.714011

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Copyright © 2021 Deng, Tan, Dai, Luo and Xu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Schematic diagram illustrating the underlying mechanism of macrophage-mediated bone formation in DBM modified by hucMSC-ECM. Briefly, DBM-ECM-induced bone regeneration depends on the osteogenic niche constructed by macrophage-derived paracrine molecules. MIF highly deposited in the DBM-ECM scaffolds activates CD74/CD44 expression in macrophages, subsequently enhances the phosphorylation of P38 and finally upregulates the expression of multiple osteoinductive cytokines, including FGF2, TGFβ3 and OSM, in macrophages, which directs the osteogenesis of BMSCs and promotes bone regeneration.