ArticleThe Journal of biological chemistry2013
The free fatty acid receptor G protein-coupled receptor 40 (GPR40) protects from bone loss through inhibition of osteoclast differentiation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 80 citations in OpenAlex.
- Marrow fatty acids in osteoporosis: metabolic insights, emerging therapeutic targets.Journal of bone and mineral metabolism · 2026Review
- Fatty Acid-Sensing G Protein-Coupled Receptors in Skeletal Metabolism.Journal of bone metabolism · 2026Article
- Dietary fiber derived short-chain fatty acids as a critical driver of the gut-bone axis in animal bone health: A review.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Review
- Role of vertebral fat fraction and R2* based on fat analysis and calculation technique in the quantitative assessment of osteoporosis.BMC musculoskeletal disorders · 2025Article
- Comprehensive Analysis of the Role of Metabolic Features in Osteoporosis: A Multi-Omics Analysis.International journal of general medicine · 2025Article
- Combination treatment with whole body vibration and simvastatin improves the early osseointegration in aged rats.Bone reports · 2024Article
- Review
- Dietary long-chain fatty acids promote colitis by regulating palmitoylation of STAT3 through CD36-mediated endocytosis.Cell death & disease · 2024Article
- Recent Advance in Regulatory Effect of GRP120 on Bone Metabolism.Aging and disease · 2023Review
- 3D-Printed Bioactive Scaffold Loaded with GW9508 Promotes Critical-Size Bone Defect Repair by Regulating Intracellular Metabolism.Bioengineering (Basel, Switzerland) · 2023Article
- A review of non-prostanoid, eicosanoid receptors: expression, characterization, regulation, and mechanism of action.Journal of cell communication and signaling · 2022Review
- Regulation of Bone Cell Differentiation and Activation by Microbe-Associated Molecular Patterns.International journal of molecular sciences · 2021Review
- Dietary ω-3 Fatty Acid Supplementation Improves Murine Sickle Cell Bone Disease and Reprograms Adipogenesis.Antioxidants (Basel, Switzerland) · 2021Article
- Pharmacology of Free Fatty Acid Receptors and Their Allosteric Modulators.International journal of molecular sciences · 2021Review
- Review
- G Protein-Coupled Receptors in Osteoarthritis: A Novel Perspective on Pathogenesis and Treatment.Frontiers in cell and developmental biology · 2021Review
- Melatonin improves the osseointegration of hydroxyapatite-coated titanium implants in senile female rats.Zeitschrift fur Gerontologie und Geriatrie · 2020Article
- Role of Metabolism in Bone Development and Homeostasis.International journal of molecular sciences · 2020Review
- Administration of alpha-lipoic acid could maintain bone mass and bone strength in senile female rats with alcohol consumption.Zeitschrift fur Gerontologie und Geriatrie · 2020Article
- Rapamycin could increase the effects of melatonin against age-dependent bone loss.Zeitschrift fur Gerontologie und Geriatrie · 2020Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
The mechanisms linking fat intake to bone loss remain unclear. By demonstrating the expression of the free fatty acid receptor G-coupled protein receptor 40 (GPR40) in bone cells, we hypothesized that this receptor may play a role in mediating the effects of fatty acids on bone remodeling. Using micro-CT analysis, we showed that GPR40(-/-) mice exhibit osteoporotic features suggesting a positive role of GPR40 on bone density. In primary cultures of bone marrow, we showed that GW9508, a GRP40 agonist, abolished bone-resorbing cell differentiation. This alteration of the receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation occurred via the inhibition of the nuclear factor κB (NF-κB) signaling pathway as demonstrated by decrease in gene reporter activity, inhibitor of κB kinase (IKKα/β) activation, inhibitor of κB (IkBα) phosphorylation, and nuclear factor of activated T cells 1 (NFATc1) expression. The GPR40-dependent effect of GW9508 was confirmed using shRNA interference in osteoclast precursors and GPR40(-/-) primary cell cultures. In addition, in vivo administration of GW9508 counteracted ovariectomy-induced bone loss in wild-type but not GPR40(-/-) mice, enlightening the obligatory role of the GPR40 receptor. Then, in a context of growing prevalence of metabolic and age-related bone disorders, our results demonstrate for the first time in translational approaches that GPR40 is a relevant target for the design of new nutritional and therapeutic strategies to counter bone complications.
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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.