Effect of metformin on ossification and inflammation of fibroblasts in ankylosing spondylitis: An in vitro study |
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| Authors: | Xiong Qin Tongmeng Jiang Sijia Liu Jiachang Tan Huayu Wu Li Zheng Jinmin Zhao |
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| Affiliation: | 1. Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;2. Collaborative Innovation Center of Guangxi Biological Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;3. Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;4. Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;5. School of Preclinical Medicine, Guangxi Medical University, Nanning, China;6. Department of Cell Biology & Genetics, School of Premedical Sciences, Guangxi Medical University, Nanning, China |
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| Abstract: | Ankylosing spondylitis (AS) is an autoimmune disease characterized by fibroblasts ossification. However, effective drug therapy for AS is lacking. As an antidiabetic drug, metformin has demonstrated an antiosteogenic effect on osteoblasts in vitro. And it is also a kind of specific agonists for adenosine 5′‐monophosphate activated protein kinase (AMPK), which is blocked in the process of AS. Given the role in antiosteogenesis and AMPK activating, metformin was investigated of its effect on fibroblasts harvested from capsular ligament of patients with femoral neck fracture and AS. Osteogenic specific makers (Alp, Bglap, Runx2, Bmp2, and Col1) in fibroblasts administered with metformin (20 μg/mL) were detected by ALP staining, alizarin red staining, qPCR, and Western blotting after 7 and 14 days of culture. Inflammation genes (il1‐β and il6) and pathway (Pi3k, Akt, and Ampk) associated markers were also evaluated. Our results showed that osteogenic specific markers were greatly downregulated and ossification was effectively inhibited in AS fibroblasts after addition of metformin. Levels of inflammation markers were also decreased by metformin. Thus, metformin exerts potent effect on suppression of ossification and inflammation in AS fibroblasts via the activation of Pi3k/Akt and AMPK pathways, which may be developed as a potential agent for treatment of AS. |
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| Keywords: | ankylosing spondylitis fibroblasts metformin ossification |
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