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Metabolic acidosis regulates RGS16 and G protein signaling in osteoblasts.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2021 Oct 01; Vol. 321 (4), pp. F424-F430. Date of Electronic Publication: 2021 Aug 16. - Publication Year :
- 2021
-
Abstract
- Chronic metabolic acidosis stimulates cell-mediated net Ca <superscript>2+</superscript> efflux from bone mediated by increased osteoblastic cyclooxygenase 2, leading to prostaglandin E <subscript>2</subscript> -induced stimulation of receptor activator of NF-κB ligand-induced osteoclastic bone resorption. Ovarian cancer G protein-coupled receptor-1 (OGR1), an osteoblastic H <superscript>+</superscript> -sensing G protein-coupled receptor, is activated by acidosis and leads to increased bone resorption. As regulator of G protein signaling (RGS) proteins limit GPCR signaling, we tested whether RGS proteins themselves are regulated by metabolic acidosis. Primary osteoblasts were isolated from neonatal mouse calvariae and incubated in physiological neutral or acidic (MET) medium. Cells were collected, and RNA was extracted for real-time PCR analysis with mRNA levels normalized to ribosomal protein L13a. RGS1 , RGS2 , RGS3 , RGS4 , RGS10 , RGS11 , and RGS18 mRNA did not differ between MET and neutral medium; however, by 30 min, MET decreased RGS16 , which persisted for 60 min and 3 h. Incubation of osteoblasts with the OGR1 inhibitor CuCl <subscript>2</subscript> inhibited the MET-induced increase in RGS16 mRNA. Gallein, a specific inhibitor of Gβγ signaling, was used to determine if downstream signaling by the βγ-subunit was critical for the response to acidosis. Gallein decreased net Ca <superscript>2+</superscript> efflux from calvariae and cyclooxygenase 2 and receptor activator of NF-κB ligand gene expression from isolated osteoblasts. These results indicate that regulation of RGS16 plays an important role in modulating the response of the osteoblastic GPCR OGR1 to metabolic acidosis and subsequent stimulation of osteoclastic bone resorption. NEW & NOTEWORTHY The results presented in this study indicate that regulation of regulator of G protein signaling 16 and G protein signaling in the osteoblast plays an important role in modulating the response of osteoblastic ovarian cancer G protein-coupled receptor 1 (OGR1) to metabolic acidosis and the subsequent stimulation of osteoclastic bone resorption. Further characterization of the regulation of OGR1 in metabolic acidosis-induced bone resorption will help in understanding bone loss in acidotic patients with chronic kidney disease.
- Subjects :
- Animals
Bicarbonates administration & dosage
Bicarbonates pharmacology
Carbon Dioxide
Cells, Cultured
GTP-Binding Proteins genetics
Hydrogen-Ion Concentration
Mice
RGS Proteins genetics
RNA genetics
RNA metabolism
Xanthenes pharmacology
Acidosis metabolism
GTP-Binding Proteins metabolism
Gene Expression Regulation drug effects
Osteoblasts metabolism
RGS Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1466
- Volume :
- 321
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 34396788
- Full Text :
- https://doi.org/10.1152/ajprenal.00166.2021