{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:19:50Z","timestamp":1792808390020,"version":"4.5.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2015,3,30]],"date-time":"2015-03-30T00:00:00Z","timestamp":1427673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Key Scientific Research Project","award":["2012CB96660"],"award-info":[{"award-number":["2012CB96660"]}]},{"name":"National Natural Science Fund","award":["81125014"],"award-info":[{"award-number":["81125014"]}]},{"name":"National Natural Science Fund","award":["81101356"],"award-info":[{"award-number":["81101356"]}]},{"name":"National Natural Science Fund","award":["81201395"],"award-info":[{"award-number":["81201395"]}]},{"name":"National Natural Science Fund","award":["81472115"],"award-info":[{"award-number":["81472115"]}]},{"name":"Zhejiang province public welfare fund","award":["2012C3112"],"award-info":[{"award-number":["2012C3112"]}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LY13C100001"],"award-info":[{"award-number":["LY13C100001"]}],"id":[{"id":"https:\/\/ror.org\/04aqat463","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Technology Development Project","award":["CXZZ201 30320172336579"],"award-info":[{"award-number":["CXZZ201 30320172336579"]}]},{"DOI":"10.13039\/501100002858","name":"Postdoctoral Foundation of China","doi-asserted-by":"crossref","award":["2013M531465"],"award-info":[{"award-number":["2013M531465"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Osteoarthritis (OA) remains an intractable clinical challenge. Few drugs are available for reversing this degenerative disease, although some promising candidates have performed well in preclinical studies. Tumor necrosis factor \u03b1 (TNF\u03b1) has been identified as a crucial effector modulating OA pathogenesis. This study aimed to investigate the therapeutic effects of Atsttrin, a novel TNF\u03b1 blocker, on OA treatment. We developed genetically modified mesenchymal stem cells (MSCs) that expressed recombinant Atsttrin (named as MSC-Atsttrin). Expression levels of ADAMTS-5, MMP13, and iNOS of human chondrocytes were analyzed when cocultured with MSC-GFP\/Atsttrin. OA animal models were induced by anterior cruciate ligament transection, and MSC-GFP\/Atsttrin were injected into the articular cavity 1 week postsurgery. The results showed that MSC-Atsttrin significantly suppressed TNF\u03b1-driven up-regulation of matrix proteases and inflammatory factors. Intra-articular injection of MSC-Atsttrin prevented the progression of degenerative changes in the surgically induced OA mouse model. Additionally, levels of detrimental matrix hydrolases were significantly diminished. Compared with nontreated OA samples at 8 weeks postsurgery, the percentages of MMP13- and ADAMTS-5-positive cells were significantly reduced from 91.33% \u00b1 9.87% to 24.33% \u00b1 5.7% (p &amp;lt; .001) and from 91.33% \u00b1 7.1% to 16.67% \u00b1 3.1% (p &amp;lt; .001), respectively. Our results thus indicated that suppression of TNF\u03b1 activity is an effective strategy for OA treatment and that intra-articular injection of MSCs-Atsttrin could be a promising therapeutic modality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The main novelty of this study is the finding of Atsttrin modified mesenchymal stem cells (MSCs-Atsttrin) for blocking osteoarthritis (OA) development within an in vivo mouse surgically induced osteoarthritis model. Because MSCs have already been widely used in the treatment of patients and have demonstrated good efficacy and safety, MSC-based Atsttrin gene therapy could be a promising modality for the treatment of OA patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.5966\/sctm.2014-0200","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T08:47:58Z","timestamp":1427878078000},"page":"523-531","source":"Crossref","is-referenced-by-count":49,"title":["Intra-Articular Transplantation of Atsttrin-Transduced Mesenchymal Stem Cells Ameliorate Osteoarthritis Development"],"prefix":"10.1093","volume":"4","author":[{"given":"Qingqing","family":"Xia","sequence":"first","affiliation":[{"name":"Center for Stem Cells and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"},{"name":"Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Center for Stem Cells and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"},{"name":"Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Stem Cells and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"},{"name":"Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Stem Cells and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"},{"name":"Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youzhi","family":"Cai","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"},{"name":"Department of Orthopedics, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Stem Cells and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"},{"name":"Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boon Chin","family":"Heng","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science & Engineering, ETH-Zurich, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Wei","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Center for Stem Cells and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"},{"name":"Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"},{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Stem Cells and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China"},{"name":"Zhejiang Provincial Key Laboratory of Tissue 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