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.

正畸治疗期间牙齿移动的加速具有挑战性，破骨细胞介导的压缩侧骨吸收是限速步骤。最近的研究表明，单核细胞/巨噬细胞表面的机械感受器，特别是粘附G蛋白偶联受体（aGPCR），在力传感中发挥着重要作用。然而，其在破骨细胞分化调节中的作用仍不清楚。在此，通过单细胞分析，我们发现CD97（一种新型机械敏感aGPCR）在巨噬细胞中表达。压缩上调 CD97 表达并抑制破骨细胞分化；而敲低 CD97 可以部分挽救破骨细胞的分化。这表明CD97可能是破骨细胞分化过程中重要的机械敏感受体。 RNA测序分析表明Rap1a/ERK信号通路介导CD97对受压下破骨细胞分化的影响。我们一致证实，服用 Rap1a 抑制剂 GGTI298 会增加破骨细胞活性，从而加速牙齿移动。总之，我们的结果表明，CD97 在正畸压力下通过 Rap1a/ERK 信号通路抑制破骨细胞分化。