ArticleAging2020
Metformin coordinates osteoblast/osteoclast differentiation associated with ischemic osteonecrosis.
Article in Aging, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Mitochondrial Quality Control in Degenerative Musculoskeletal Diseases: Signaling Networks and Therapeutic Landscapes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Metformin as a Metabolic Reprogramming Interface in Host-Pathogen and Bone Microenvironment Crosstalk: A Dual-Target Strategy Against Antimicrobial Resistance and Osteoporotic Bone Loss.Antibiotics (Basel, Switzerland) · 2026Review
- Dose-Dependent Impact of Metformin on Osteoblast-Specific Biomarkers in Cultured Rat Primary Osteoblasts.Physiological research · 2026Article
- Effect of metformin on inflammation and bone damage in a rat model of medication-related osteonecrosis of the jaw.European journal of oral sciences · 2026Article
- From Diabetes to Degenerative Diseases: The Multifaceted Action of Metformin.International journal of molecular sciences · 2025Review
- V-ATPase and Lysosomal Energy Sensing in Periodontitis and Medicine-Related Osteonecrosis of the Jaw.Biomolecules · 2025Review
- Recent Research on the Role of Phytochemicals from Ginseng in Management of Osteosarcoma, Osteoporosis, and Osteoarthritis.Nutrients · 2025Review
- Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025Review
- AMPK signaling in osteoarthritis: from mechanisms to targeted therapeutics.Frontiers in pharmacology · 2025Review
- Activation of the LKB1/AMPK/HIF-1α Pathway by Metformin to Promote Neovascularisation in Cerebral Ischaemia.Neurochemical research · 2024Article
- Pathological mechanisms and related markers of steroid-induced osteonecrosis of the femoral head.Annals of medicine · 2024Review
- Moldable Alginate/Hydroxyapatite Hydrogel Loaded with Metformin Enhanced Regeneration of the Rabbit Mandibular Defects.Journal of maxillofacial and oral surgery · 2024Article
- Angiogenesis of Avascular Necrosis of the Femoral Head: A Classic Treatment Strategy.Biomedicines · 2024Review
- Medication-related osteonecrosis of the jaw: evolving research for multimodality medical management.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Review
- The Differential Effect of Metformin on Osteocytes, Osteoblasts, and Osteoclasts.Current osteoporosis reports · 2023Review
- Exploring the role and mechanism of Fuzi decoction in the treatment of osteoporosis by integrating network pharmacology and experimental verification.Journal of orthopaedic surgery and research · 2023Article
- Metformin regulates bone marrow stromal cells to accelerate bone healing in diabetic mice.eLife · 2023Article
- The Potential Therapeutic Role of Metformin in Diabetic and Non-Diabetic Bone Impairment.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- The Function of Metformin in Aging-Related Musculoskeletal Disorders.Frontiers in pharmacology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we aimed to identify a candidate drug that can activate endogenous Angiopoietin 1 (Ang1) expression via drug repositioning as a pharmacological treatment for avascular osteonecrosis. After incubation with 821 drugs from the Food and Drug Administration (FDA)-approved drug library, Ang1 expression in U2OS cell culture media was examined by ELISA. Metformin, the first-line medication for treatment of type 2 diabetes, was selected as a candidate for in vitro and in vivo experimental evaluation. Ang1 was induced, and alkaline phosphatase activity was increased by metformin treatment in U2OS and MG63 cells. Wound healing and migration assay showed increased osteoblastic cell mobility by metformin treatment in U2OS and MG63 cells. Metformin upregulated expression of protein markers for osteoblastic differentiation in U2OS and MG63 cells but inhibited osteoclastic differentiation in Raw264.7 cells. Metformin (25 mg/kg) protected against ischemic necrosis in the epiphysis of the rat femoral head by maintaining osteoblast/osteocyte function and vascular density but inhibiting osteoclast activity in the necrotic femoral head. These findings provide novel insight into the specific biomarkers that are targeted and regulated by metformin in osteoblast differentiation and contribute to understanding the effects of these FDA-approved small-molecule drugs as novel therapeutics for ischemic osteonecrosis.
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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.