RGS18 Acts as a Negative Regulator of Osteoclastogenesis by Modulating the Acid-Sensing OGR1/NFAT Signaling Pathway

• DOI: 10.1359/jbmr.070612
• Publication Date: 2007-06-18T19:58:44Z
• Authors: Kaori Iwai; Masato Koike; Shiro Ohshima; Kunio Miyatake; Yasuo Uchiyama; Yukihiko Saeki; Masaru Ishii
• Keywords: NFAT; Monocyte

We showed that RGS18, a myeloid lineage-specific RGS protein is inhibited after activation of the RANK/RANKL system, negative regulator osteoclastogenesis. RGS18 acts through an external acidosis-sensing osteoclastogenic mechanism OGR1/NFAT pathway.Osteoclasts are bone-resorbing multinuclear giant cells differentiated from mononuclear macrophage/monocyte lineage precursors stimulated by system. The regulators G-protein signaling (RGS) family diverse group proteins accelerate intrinsic GTP hydrolysis on heterotrimeric alpha subunits and play crucial roles in physiological regulation G-protein-mediated cell various tissues organs. examined expression function protein, during osteoclastogenesis.A line, RAW264.7, primary osteoclast precursor monocytes derived mouse bone marrow cultured with macrophage-colony stimulating factor (M-CSF) (bone marrow-derived [BMMs]) were used this study. Both types differentiate into osteoclast-like RANKL. Expression different proteins, including was assessed gene-specific RT-PCR. subcellular distribution native osteoclasts tissues, as well RAW264.7 cells, immunohistochemistry using specific polyclonal antibody. Short interfering RNA against to inhibit endogenous these types. Activation NFATc1, transcription factor, acidosis visualizing nuclear localization NFATc1 visualized anti-NFATc1 antibody.RAW264.7 BMM both expressed mRNA for 10 mammalian RGS18. significantly RANKL types, inhibition interference prominently enhanced osteoclastogenesis stimulation effect reversed blocking proton-sensing OGR1 signaling, overexpression exogenous extracellular acidosis-mediated activation. Immunohistochemical studies revealed vivo.RGS18 acidosis-induced pathway, stimulates inhibiting Therefore, results suggest novel control proteins.