Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Department of Obstetrics and Gynecology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Prostaglandins Leukot Essent Fatty Acids. 2022 Jul;182:102457. doi: 10.1016/j.plefa.2022.102457. Epub 2022 Jun 3.
Bone remodeling is precisely regulated mainly by osteoblasts and osteoclasts. Although some G-protein coupled receptors (GPCRs) were reported to play roles in osteoblast function, little is known about the roles in osteoclasts. In this study, we found, for the first time, that the expression of GPR110 increased during osteoclastogenesis. GPR110 belongs to adhesion GPCR and was the functional receptor of N-docosahexaenoyl ethanolamine (also called synaptamide). Synaptamide suppressed osteoclastogenesis induced by receptor activator of nuclear factor-kappa B ligand. Considering that synaptamide is the endogenous metabolite of DHA, we hypothesized that DHA may inhibit osteoclastogenesis by affecting synaptamide/GPR110 signaling. But GPR110 knockout and subsequent rescue experiments revealed a pivotal role of GPR110 in the attenuation of osteoclastogenesis by synaptamide but not by DHA. These results suggest that synaptamide/GPR110 signaling negatively regulates osteoclastogenesis. Our study suggested that ligands of GPR110, such as synaptamide, might be a useful drug for osteoporotic patients.
骨重塑主要由成骨细胞和破骨细胞精确调节。虽然一些 G 蛋白偶联受体（GPCRs）被报道在成骨细胞功能中发挥作用，但对于破骨细胞中的作用知之甚少。在这项研究中，我们首次发现 GPR110 的表达在破骨细胞发生过程中增加。GPR110 属于黏附 GPCR，是 N-二十二碳六烯酰乙醇胺（也称为突触酰胺）的功能性受体。突触酰胺抑制核因子-κB 配体受体激活剂诱导的破骨细胞发生。考虑到突触酰胺是 DHA 的内源性代谢物，我们假设 DHA 可能通过影响突触酰胺/GPR110 信号来抑制破骨细胞发生。但 GPR110 敲除和随后的挽救实验表明，突触酰胺而不是 DHA 通过 GPR110 调节破骨细胞发生的衰减中起着关键作用。这些结果表明突触酰胺/GPR110 信号负向调节破骨细胞发生。我们的研究表明，GPR110 的配体，如突触酰胺，可能是骨质疏松症患者的一种有用药物。
