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. 2020 Sep 2;8:32. doi: 10.1038/s41413-020-00106-0

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© The Author(s) 2020

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. 9 — Illustration of this study’s results and a working model. BMP signaling enhances the Rankl/Opg expression ratio in cells of the osteoblastic lineage to promote osteoclastic bone resorption in bone remodeling. Moreover, the BMP-Smad pathway directly induces Atoh8 in immature osteoblasts. Atoh8 interacts with Runx2 and inhibits Runx2 transcriptional activity to suppress autoregulation of Runx2 and subsequent osteoblastic differentiation, as well as the Rankl/Opg expression ratio, thereby regulating the osteoclast number negatively to prevent excessive BMP-mediated bone resorption (left panel). The enhanced Runx2 activity in Atoh8-KO mice likely limited osteoblast maturation to maintain bone formation, while Runx2 increased the Rankl/Opg expression ratio to promote bone resorption and loss (right panel)