Effect of metformin on ossification and inflammation of fibroblasts in ankylosing spondylitis: An in vitro study
| Autor: | Jiachang Tan, Jinmin Zhao, Tongmeng Jiang, Li Zheng, Xiong Qin, Huayu Wu, Si-Jia Liu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Cell Culture Techniques Inflammation AMP-Activated Protein Kinases Biochemistry Mice 03 medical and health sciences Osteogenesis Internal medicine medicine Animals Humans Spondylitis Ankylosing Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Ankylosing spondylitis Ossification business.industry Interleukins AMPK Cell Biology Fibroblasts medicine.disease Metformin Femoral Neck Fractures RUNX2 030104 developmental biology Endocrinology Gene Expression Regulation Case-Control Studies medicine.symptom business Biomarkers medicine.drug |
| Zdroj: | Journal of Cellular Biochemistry. 119:1074-1082 |
| ISSN: | 1097-4644 0730-2312 |
| DOI: | 10.1002/jcb.26275 |
| Popis: | 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 anti-osteogenic effect on osteoblasts in vitro. And it is also a kind of specific agonists for AMPK, which is blocked in the process of AS. Given the role in anti-osteogenesis and AMPK activating, metformin was investigated of its effect on fibroblasts harvested from capsular ligament of patients with femoral neck fracture and ankylosing spondylitis. Osteogenic specific makers (Alp, Bglap, Runx2, Bmp2, and Col1) in fibroblasts administered with metformin 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. This article is protected by copyright. All rights reserved |
| Databáze: | OpenAIRE |
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