ArticleThe Journal of clinical investigation2002
Anabolic effects of a G protein-coupled receptor kinase inhibitor expressed in osteoblasts.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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.
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Who cites it
13 citing papers in PubMed, 37 citations in OpenAlex.
- G protein-coupled receptor signaling in osteogenic bone mesenchymal stem/stromal cells.Frontiers in cell and developmental biology · 2026Review
- Article
- Effect of Regulator of G Protein Signaling Proteins on Bone.Frontiers in endocrinology · 2022Review
- GPR125 positively regulates osteoclastogenesis potentially through AKT-NF-κB and MAPK signaling pathways.International journal of biological sciences · 2022Article
- Osteogenesis Is Improved by Low Tumor Necrosis Factor Alpha Concentration through the Modulation of Gs-Coupled Receptor Signals.Molecular and cellular biology · 2017Article
- Control of bone remodeling by the peripheral sympathetic nervous system.Calcified tissue international · 2014Review
- G-protein-coupled receptor kinase 2 and hypertension: molecular insights and pathophysiological mechanisms.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2013Review
- P2Y(2) receptors and GRK2 are involved in oscillatory fluid flow induced ERK1/2 responses in chondrocytes.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2011Article
- Role of PTH1R internalization in osteoblasts and bone mass using a phosphorylation-deficient knock-in mouse model.The Journal of endocrinology · 2010Article
- A beta-arrestin-biased agonist of the parathyroid hormone receptor (PTH1R) promotes bone formation independent of G protein activation.Science translational medicine · 2009Article
- Inhibition of WNT signaling by G protein-coupled receptor (GPCR) kinase 2 (GRK2).Molecular endocrinology (Baltimore, Md.) · 2009Article
- Osteoblast-derived PTHrP is a potent endogenous bone anabolic agent that modifies the therapeutic efficacy of administered PTH 1-34.The Journal of clinical investigation · 2005Article
- Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes.Diabetologia · 2004Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
G protein-coupled receptors (GPCRs) play a key role in regulating bone remodeling. Whether GPCRs exert anabolic or catabolic osseous effects may be determined by the rate of receptor desensitization in osteoblasts. Receptor desensitization is largely mediated by direct phosphorylation of GPCR proteins by a family of enzymes termed GPCR kinases (GRKs). We have selectively manipulated GRK activity in osteoblasts in vitro and in vivo by overexpressing a GRK inhibitor. We found that expression of a GRK inhibitor enhanced parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor-stimulated cAMP generation and inhibited agonist-induced phosphorylation of this receptor in cell culture systems, consistent with attenuation of receptor desensitization. To determine the effect of GRK inhibition on bone formation in vivo, we targeted the expression of a GRK inhibitor to mature osteoblasts using the mouse osteocalcin gene 2 (OG2) promoter. Transgenic mice demonstrated enhanced bone remodeling as well as enhanced urinary excretion of the osteoclastic activity marker dexoypyridinoline. Both osteoprotegrin and OPG ligand mRNA levels were altered in calvaria of transgenic mice in a pattern that would promote osteoclast activation. The predominant effect of the transgene, however, was anabolic, as evidenced by an increase in bone density and trabecular bone volume in the transgenic mice compared with nontransgenic littermate controls.
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What OpenQuestion holds
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.