ArticleStem cell research & therapy2021
PPARβ/δ accelerates bone regeneration in diabetic mellitus by enhancing AMPK/mTOR pathway-mediated autophagy.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Engineering MSC-exosomes for diabetic bone regeneration: from mechanism to delivery.Stem cell research & therapy · 2026Review
- Starvation-induced NEDD4-mediated autophagy in BMSCs.Biomedical reports · 2026Article
- Naringin-based hydrogel decorated 3D printed scaffold modulates immunity and angiogenesis for diabetic bone regeneration.Regenerative biomaterials · 2026Article
- Mechanical Loading Induces NRF2 Nuclear Translocation to Epigenetically Remodel Oxidative Stress Defense in Osteocytes.Antioxidants (Basel, Switzerland) · 2025Article
- Dexmedetomidine Alleviates Abdominal Aortic Aneurysm by Activating Autophagy Via AMPK/mTOR Pathway.Cardiovascular drugs and therapy · 2025Article
- Potential Signal Pathways and Therapeutic Effects of Mesenchymal Stem Cell on Oxidative Stress in Diseases.Current pharmaceutical design · 2025Review
- The Critical Role of Autophagy in the Pathogenesis of Diabetic Osteoporosis: Mechanisms and Therapeutic Measures.Drug design, development and therapy · 2025Review
- A blood glucose fluctuation-responsive delivery system promotes bone regeneration and the repair function of Smpd3-reprogrammed BMSC-derived exosomes.International journal of oral science · 2024Article
- Functionalized 3D-printed GelMA/Laponite hydrogel scaffold promotes BMSCs recruitment through osteoimmunomodulatory enhance osteogenic via AMPK/mTOR signaling pathway.Materials today. Bio · 2024Article
- Inhibition of miR-542-3p augments autophagy to promote diabetic corneal wound healing.Eye and vision (London, England) · 2024Article
- Topical hADSCs-HA Gel Promotes Skin Regeneration and Angiogenesis in Pressure Ulcers by Paracrine Activating PPARβ/δ Pathway.Drug design, development and therapy · 2024Article
- O304 alleviates abdominal aortic aneurysm formation via AMPK/mTOR/MMP pathway activation.Frontiers in pharmacology · 2024Article
- An Overview of the Role of Peroxisome Proliferator-activated Receptors in Liver Diseases.Journal of clinical and translational hepatology · 2023Review
- Recent progress in bone-repair strategies in diabetic conditions.Materials today. Bio · 2023Review
- Constitutively activated AMPKα1 protects against skeletal aging in mice by promoting bone-derived IGF-1 secretion.Cell proliferation · 2023Article
- Zoledronate Promotes Peri-Implant Osteogenesis in Diabetic Osteoporosis by the AMPK Pathway.Calcified tissue international · 2023Article
- mTOR Signaling Pathway in Bone Diseases Associated with Hyperglycemia.International journal of molecular sciences · 2023Review
- Osteogenesis of bone marrow mesenchymal stem cell in hyperglycemia.Frontiers in endocrinology · 2023Review
- Lignin/Puerarin Nanoparticle-Incorporated Hydrogel Improves Angiogenesis through Puerarin-Induced Autophagy Activation.International journal of nanomedicine · 2023Article
- Ginsenoside Rg1 Ameliorates Pancreatic Injuries via the AMPK/mTOR Pathway in vivo and in vitro.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiabetic patients are more vulnerable to skeletal complications. Peroxisome proliferators-activated receptor (PPAR) β/δ has a positive regulatory effect on bone turnover under physiologic glucose concentration; however, the regulatory effect in diabetes mellitus has not been investigated yet. Herein, we explored the effects of PPARβ/δ agonist on the regeneration of diabetic bone defects and the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) under a pathological high-glucose condition.
methodsWe detected the effect of PPARβ/δ agonist on osteogenic differentiation of rBMSCs in vitro and investigated the bone healing process in diabetic rats after PPARβ/δ agonist treatment in vivo. RNA sequencing was performed to detect the differentially expressed genes and enriched pathways. Western blot was performed to detect the autophagy-related protein level. Laser confocal microscope (LSCM) and transmission electron microscope (TEM) were used to observe the formation of autophagosomes.
resultsOur results demonstrated that the activation of PPARβ/δ can improve the osteogenic differentiation of rBMSCs in high-glucose condition and promote the bone regeneration of calvarial defects in diabetic rats, while the inhibition of PPARβ/δ alleviated the osteogenic differentiation of rBMSCs. Mechanistically, the activation of PPARβ/δ up-regulates AMPK phosphorylation, yielding mTOR suppression and resulting in enhanced autophagy activity, which further promotes the osteogenic differentiation of rBMSCs in high-glucose condition. The addition of AMPK inhibitor Compound C or autophagy inhibitor 3-MA inhibited the osteogenesis of rBMSCs in high-glucose condition, suggesting that PPARβ/δ agonist promotes osteogenic differentiation of rBMSCs through AMPK/mTOR-regulated autophagy.
conclusionIn conclusion, our study demonstrates the potential role of PPARβ/δ as a molecular target for the treatment of impaired bone quality and delayed bone healing in diabetic patients for the first time.
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