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. 2021 Oct 29;9:747057. doi: 10.3389/fcell.2021.747057

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Copyright © 2021 Melnik, Hofmann, Gabler, Hecht and Richter.

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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Mechanism for the pro-chondrogenic effects caused by miR-181a. MiR-181a targets RSPO2 which is a strong agonist of canonical WNT signaling and an inhibitor of BMP signaling. Loss of RSPO2 results in activation of BMP signaling manifested by increased phospho-SMAD1/5/9 and SOX9 accumulation, as well as in inhibition of canonical WNT target gene expression, AXIN2, thus, affecting the balance between WNT and BMP signaling to favor chondral outcome. Thin arrows indicate regulations of the highlighted pathways, and thick arrows display the effects caused by miR-181a; red, downregulation; green, upregulation.