CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression

Wen Wang1,2, Qian Wang3, Shiying Sun1,2, Pengfei Zhang1,2, Yuyu Li3, Weimin Lin3, Qiwen Li3, Xiao Zhang3, Zhe Ma1,4, Haiyan Lu1,2

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International Journal of Oral Science ›› 2024, Vol. 16 ›› Issue (0) : 12. DOI: 10.1038/s41368-023-00272-x

CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression

  • Wen Wang1,2, Qian Wang3, Shiying Sun1,2, Pengfei Zhang1,2, Yuyu Li3, Weimin Lin3, Qiwen Li3, Xiao Zhang3, Zhe Ma1,4, Haiyan Lu1,2
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Abstract

Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force sensing. However, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation; while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion, our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

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Wen Wang, Qian Wang, Shiying Sun, Pengfei Zhang, Yuyu Li, Weimin Lin, Qiwen Li, Xiao Zhang, Zhe Ma, …Haiyan Lu. CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression. International Journal of Oral Science, 2024, 16(0): 12 https://doi.org/10.1038/s41368-023-00272-x

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