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Metformin coordinates osteoblast/osteoclast differentiation associated with ischemic osteonecrosis
See-Hyoung Park1, Mi-Ae Kang2, Young Jae Moon3
1Department of Bio and Chemical Engineering, Hongik University, Sejong, Korea.
Aging
|February 12, 2020
Summary
Metformin, a diabetes drug, was repurposed to treat avascular osteonecrosis by activating Angiopoietin 1 (Ang1) expression. This study demonstrates metformin
Area of Science:
- Biomedical research
- Pharmacology
- Orthopedics
Background:
- Avascular osteonecrosis is a debilitating bone disease with limited treatment options.
- Drug repositioning offers a strategy to identify novel therapeutics for various conditions.
- Endogenous Angiopoietin 1 (Ang1) plays a crucial role in bone health and vascularization.
Purpose of the Study:
- To identify FDA-approved drugs that can activate Angiopoietin 1 (Ang1) expression for treating avascular osteonecrosis.
- To evaluate metformin as a potential therapeutic agent for avascular osteonecrosis through drug repositioning.
- To investigate the effects of metformin on osteoblast differentiation and osteoclast activity.
Main Methods:
- Screening of 821 FDA-approved drugs for their ability to induce Ang1 expression in U2OS cell culture using ELISA.
- In vitro studies using U2OS and MG63 cells to assess metformin's effects on Ang1 induction, alkaline phosphatase activity, cell migration, and osteoblastic/osteoclastic differentiation.
- In vivo studies using a rat femoral head model to evaluate metformin's protective effects against ischemic necrosis.
Main Results:
- Metformin was identified as a candidate drug that significantly increased Ang1 expression and alkaline phosphatase activity in osteoblast cell lines.
- Metformin enhanced osteoblastic cell mobility, upregulated osteoblastic differentiation markers, and inhibited osteoclastic differentiation.
- In vivo, metformin (25 mg/kg) protected against femoral head necrosis by preserving osteoblast/osteocyte function and vascular density while suppressing osteoclast activity.
Conclusions:
- Metformin demonstrates therapeutic potential for avascular osteonecrosis by modulating Ang1 expression and influencing osteoblast and osteoclast activity.
- This study highlights the efficacy of drug repositioning in discovering novel treatments for bone diseases.
- Metformin's specific molecular targets in osteoblast differentiation offer new insights for avascular osteonecrosis treatment strategies.
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