Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Collaborative Innovation Center of Guangxi Biological Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
J Cell Biochem. 2018 Jan;119(1):1074-1082. doi: 10.1002/jcb.26275. Epub 2017 Aug 23.
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.
强直性脊柱炎（AS）是一种以成纤维细胞骨化为特征的自身免疫性疾病。然而，目前针对 AS 还缺乏有效的药物治疗。二甲双胍作为一种抗糖尿病药物，在体外对成骨细胞具有抗成骨作用。同时，它也是一种腺苷 5'-单磷酸激活蛋白激酶（AMPK）的特异性激动剂，而 AMPK 在 AS 发生过程中受到抑制。鉴于其在抗成骨作用和激活 AMPK 方面的作用，研究人员研究了二甲双胍对取自股骨颈骨折和 AS 患者囊韧带的成纤维细胞的影响。通过碱性磷酸酶染色、茜素红染色、qPCR 和 Western blot 检测培养 7 天和 14 天后，给予二甲双胍（20μg/ml）的成纤维细胞中骨形成特异性标志物（ALP、Bglap、Runx2、Bmp2 和 Col1）的表达情况。还评估了与炎症相关的基因（il1-β 和 il6）和通路（Pi3k、Akt 和 Ampk）的标志物。结果表明，加入二甲双胍后，AS 成纤维细胞中的成骨特异性标志物表达明显下调，骨化得到有效抑制。二甲双胍还降低了炎症标志物的水平。因此，二甲双胍通过激活 Pi3k/Akt 和 AMPK 通路，对 AS 成纤维细胞的骨化和炎症具有显著抑制作用，可能成为治疗 AS 的潜在药物。
