ArticleKidney international2016
Increased bone density in mice lacking the proton receptor OGR1.
Article in Kidney international, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07473713 (Veverimer to Decrease Net Acid Excretion and Bone Resorption in Adults With Osteopenia), which is not on this map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Veverimer to Decrease Net Acid Excretion and Bone Resorption in Adults With Osteopenia: a Dose-finding Randomized Controlled Trial
Who cites it
19 citing papers in PubMed, 46 citations in OpenAlex.
- Unveiling the impact of colonic pH and pH-sensing receptors in blood pressure regulation.Gut microbes · 2026Review
- Acidic extracellular pH-induced PTH secretion in male mouse parathyroids is OGR1-dependent.Endocrinology · 2026Article
- Review
- Article
- pH and proton-sensitive receptors in brain ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Preclinical and Clinical Evidence of Effect of Acid on Bone Health.Advances in chronic kidney disease · 2022Review
- Effects of acid on bone.Kidney international · 2022Review
- Physiological relevance of proton-activated GPCRs.Pflugers Archiv : European journal of physiology · 2022Review
- Metabolic acidosis regulates RGS16 and G protein signaling in osteoblasts.American journal of physiology. Renal physiology · 2021Article
- Differential Roles of Extracellular Histidine Residues of GPR68 for Proton-Sensing and Allosteric Modulation by Divalent Metal Ions.Biochemistry · 2020Article
- Acid-base balance of the diet-implications for bone and muscle.European journal of clinical nutrition · 2020Review
- Whole body deletion of Gpr68 does not change hematopoietic stem cell function.Stem cell research · 2020Article
- Article
- G protein-coupled receptor 68 increases the number of B lymphocytes.American journal of blood research · 2020Article
- LMCD1 promotes osteogenic differentiation of human bone marrow stem cells by regulating BMP signaling.Cell death & disease · 2019Article
- GPR68: An Emerging Drug Target in Cancer.International journal of molecular sciences · 2019Review
- The role of GPCRs in bone diseases and dysfunctions.Bone research · 2019Review
- Deletion of proton-sensing receptor GPR4 associates with lower blood pressure and lower binding of angiotensin II receptor in SFO.American journal of physiology. Renal physiology · 2016Article
- The Roles of Acidosis in Osteoclast Biology.Frontiers in physiology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic metabolic acidosis stimulates cell-mediated calcium efflux from bone through osteoblastic prostaglandin E2-induced stimulation of receptor activator of NF-kB ligand leading to increased osteoclastic bone resorption. Osteoblasts express the proton-sensing G-protein-coupled receptor OGR1, which activates inositol phosphate-mediated intracellular calcium. Proton-induced osteoblastic intracellular calcium signaling requires ovarian cancer G-protein-coupled receptor 1 (OGR1), suggesting that OGR1 is the sensor activated during acidosis to cause bone resorption. Growing mice produce large amounts of metabolic acids, which must be buffered, primarily by bone, before excretion by the kidney. Here we tested whether lack of OGR1 inhibits proton-induced bone resorption by measuring bone mineral density by micro-computed tomography and histomorphometry in 8-week-old male OGR1(-/-) and C57/Bl6 wild type mice. OGR1(-/-) mice have normal skeletal development with no atypical gross phenotype. Trabecular and cortical bone volume was increased in tibiae and vertebrae from OGR1(-/-). There were increased osteoblast numbers on the cortical and trabecular surfaces of tibiae from OGR1(-/-) mice, increased endocortical and trabecular bone formation rates, and osteoblastic gene expression. Osteoclast numbers and surface were increased in tibiae of OGR1(-/-) mice. Thus, in rapidly growing mice, lack of OGR1 leads to increased bone mass with increased bone turnover and a greater increase in bone formation than resorption. This supports the important role of the proton receptor OGR1 in the response of bone to protons.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.