ArticleThe Journal of biological chemistry2012
Thiazolidinediones induce osteocyte apoptosis by a G protein-coupled receptor 40-dependent mechanism.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 86 citations in OpenAlex.
- Bone health in diabetes mellitus.Reviews in endocrine & metabolic disorders · 2026Review
- Therapeutic potential of low-dose rosiglitazone in periodontitis: attenuation of inflammation and bone loss through macrophage reprogramming.BMC oral health · 2026Article
- Fatty Acid-Sensing G Protein-Coupled Receptors in Skeletal Metabolism.Journal of bone metabolism · 2026Article
- Cladosporols and PPARγ: Same Gun, Same Bullet, More Targets.Biomolecules · 2024Review
- Cryo-electron microscopy for GPCR research and drug discovery in endocrinology and metabolism.Nature reviews. Endocrinology · 2024Review
- Peroxisome proliferator activated receptor-γ in osteoblasts controls bone formation and fat mass by regulating sclerostin expression.iScience · 2023Article
- 3D-Printed Bioactive Scaffold Loaded with GW9508 Promotes Critical-Size Bone Defect Repair by Regulating Intracellular Metabolism.Bioengineering (Basel, Switzerland) · 2023Article
- GPCR in Adipose Tissue Function-Focus on Lipolysis.Biomedicines · 2023Review
- Iron metabolism and ferroptosis in diabetic bone loss: from mechanism to therapy.Frontiers in nutrition · 2023Review
- Schizophrenia: a disorder of broken brain bioenergetics.Molecular psychiatry · 2022Review
- Thiazolidinediones (TZDs) enhance insulin secretory response via GPR40 and adenylate cyclase (AC).Journal of cellular physiology · 2021Article
- Pharmacology of Free Fatty Acid Receptors and Their Allosteric Modulators.International journal of molecular sciences · 2021Review
- Sclerostin-Neutralizing Antibody Treatment Rescues Negative Effects of Rosiglitazone on Mouse Bone Parameters.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Free Fatty Acid Receptor 1 Signaling Contributes to Migration, MMP-9 Activity, and Expression of IL-8 Induced by Linoleic Acid in HaCaT Cells.Frontiers in pharmacology · 2020Article
- CORR® ORS Richard A. Brand Award: Disruption in Peroxisome Proliferator-Activated Receptor-γ (PPARG) Increases Osteonecrosis Risk Through Genetic Variance and Pharmacologic Modulation.Clinical orthopaedics and related research · 2019Article
- Physiologic and pathologic effects of dietary free fatty acids on cells of the joint.Annals of the New York Academy of Sciences · 2019Review
- Diabetes pharmacotherapy and effects on the musculoskeletal system.Diabetes/metabolism research and reviews · 2019Review
- The role of GPCRs in bone diseases and dysfunctions.Bone research · 2019Review
- Diabetes Mellitus-induced Bone Fragility.Internal medicine (Tokyo, Japan) · 2018Article
- Diabetes, bone and glucose-lowering agents: basic biology.Diabetologia · 2017 · on this mapReview
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thiazolidinediones (TZDs) represent an interesting treatment of type 2 diabetes mellitus. However, adverse effects such as heart problems and bone fractures have already been reported. Previously, we reported that pioglitazone and rosiglitazone induce osteocyte apoptosis and sclerostin up-regulation; however, the molecular mechanisms leading to such effects are unknown. In this study, we found that TZDs rapidly activated Erk1/2 and p38. These activations were mediated through Ras proteins and GPR40, a receptor expressed on the surface of osteocytes. Activation of this pathway led only to osteocyte apoptosis but not sclerostin up-regulation. On the other hand, TZDs were capable of activating peroxisome proliferator-activated receptor-γ, and activation of this signaling pathway led to sclerostin up-regulation but not osteocyte apoptosis. This study demonstrates two distinct signaling pathways activated in osteocytes in response to TZDs that could participate in the observed increase in fractures in TZD-treated patients.
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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.