{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T11:49:05Z","timestamp":1794052145194,"version":"4.8.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,8,23]],"date-time":"2017-08-23T00:00:00Z","timestamp":1503446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472054"],"award-info":[{"award-number":["81472054"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:label\/><jats:p>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\u2032\u2010monophosphate 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 (<jats:italic>Alp<\/jats:italic>, <jats:italic>Bglap<\/jats:italic>, <jats:italic>Runx2<\/jats:italic>, <jats:italic>Bmp2<\/jats:italic>, and <jats:italic>Col1<\/jats:italic>) in fibroblasts administered with metformin (20\u2009\u03bcg\/mL) were detected by ALP staining, alizarin red staining, qPCR, and Western blotting after 7 and 14 days of culture. Inflammation genes (<jats:italic>il1\u2010\u03b2<\/jats:italic> and <jats:italic>il6<\/jats:italic>) and pathway (<jats:italic>Pi3k<\/jats:italic>, <jats:italic>Akt<\/jats:italic>, and <jats:italic>Ampk<\/jats:italic>) 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.26275","type":"journal-article","created":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T11:28:30Z","timestamp":1499772510000},"page":"1074-1082","source":"Crossref","is-referenced-by-count":38,"title":["Effect of metformin on ossification and inflammation of fibroblasts in ankylosing spondylitis: An in vitro study"],"prefix":"10.1002","volume":"119","author":[{"given":"Xiong","family":"Qin","sequence":"first","affiliation":[{"name":"Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Collaborative Innovation Center of Guangxi Biological Medicine The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Department of Orthopaedics Trauma and Hand Surgery The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Guangxi Key Laboratory of Regenerative Medicine The First Affiliated Hospital of Guangxi Medical University Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongmeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Collaborative Innovation Center of Guangxi Biological Medicine The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Department of Orthopaedics Trauma and Hand Surgery The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Guangxi Key Laboratory of Regenerative Medicine The First Affiliated Hospital of Guangxi Medical University Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Liu","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Guangxi Biological Medicine The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Guangxi Key Laboratory of Regenerative Medicine The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"School of Preclinical Medicine Guangxi Medical University Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachang","family":"Tan","sequence":"additional","affiliation":[{"name":"Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Collaborative Innovation Center of Guangxi Biological Medicine The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Department of Orthopaedics Trauma and Hand Surgery The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Guangxi Key Laboratory of Regenerative Medicine The First Affiliated Hospital of Guangxi Medical University Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology &amp; Genetics School of Premedical Sciences Guangxi Medical University Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zheng","sequence":"additional","affiliation":[{"name":"Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Collaborative Innovation Center of Guangxi Biological Medicine The First Affiliated Hospital of Guangxi Medical University Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Collaborative Innovation Center of Guangxi Biological Medicine The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Department of Orthopaedics Trauma and Hand Surgery The First Affiliated Hospital of Guangxi Medical University Nanning China"},{"name":"Guangxi Key Laboratory of Regenerative Medicine The First Affiliated Hospital of Guangxi Medical University Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3171\/FOC\/2008\/24\/1\/E2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAJ.0b013e318294457f"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2014.10.024"},{"key":"e_1_2_7_5_1","first-page":"1719","article-title":"Long\u2010term safety and efficacy of infliximab for the treatment of ankylosing spondylitis","volume":"11","author":"Elalouf O","year":"2015","journal-title":"Ther Clin Risk Manag"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.7748\/ns2013.12.28.16.52.e7807"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2013.02.004"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.5582\/bst.2011.v5.2.46"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/107632702760184709"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15116"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/6365857"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.06.003"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.490"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12950-016-0114-7"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.23937\/2469-5726\/1510005"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.23206"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.090732"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.02.030"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.08.034"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/453940"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21917"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2016.01.002"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780270401"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2009.090414"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600645R"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.455"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2014.07.005"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.275"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18010229"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728221003774135"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.3109\/08923973.2015.1122619"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.160584"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14982"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep32771"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8206281"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.09.091"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.39"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20160483"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.26275","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.26275","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcb.26275","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.26275","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,13]],"date-time":"2025-04-13T18:20:35Z","timestamp":1744568435000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.26275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,23]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1002\/jcb.26275"],"URL":"https:\/\/doi.org\/10.1002\/jcb.26275","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,23]]}}}