{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:59:17Z","timestamp":1790553557845,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T00:00:00Z","timestamp":1453680000000},"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":"crossref","award":["81271951"],"award-info":[{"award-number":["81271951"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81401850"],"award-info":[{"award-number":["81401850"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Guangdong Higher Education Institutes, Engineering Technology Research Center for Comprehensive Diagnosis and Treatment of Ankylosing Spondylitis","award":["GCZX-A1301"],"award-info":[{"award-number":["GCZX-A1301"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To study the osteogenic differentiation capacity of bone marrow\u2013derived mesenchymal stem cells (BM\u2010MSCs) from patients with ankylosing spondylitis (AS) and to investigate the mechanisms of abnormal osteogenic differentiation of BM\u2010MSCs in AS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>BM\u2010MSCs from healthy donors (HD\u2010MSCs) and patients with AS (AS\u2010MSCs) were cultured in osteogenic differentiation medium for 0\u201321 days, after which their osteogenic differentiation capacity was determined using alizarin red S and alkaline phosphatase assays. Gene expression levels of osteoblastic markers and related cytokines were detected by high\u2010throughput quantitative reverse transcription\u2013polymerase chain reaction. Enzyme\u2010linked immunosorbent assay was performed to detect protein levels of bone morphogenetic protein 2 (BMP\u20102) and Noggin in the cell culture supernatant. The activation of Smad1\/5\/8 and MAPK signaling pathways was measured by Western blotting. The balance between BMP\u20102 and Noggin expression was regulated using lentiviruses encoding short hairpin RNA and exogenous Noggin, respectively, which enabled evaluation of how this balance affected osteogenic differentiation of AS\u2010MSCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AS\u2010MSCs outperformed HD\u2010MSCs in osteogenic differentiation capacity. During osteogenic differentiation, AS\u2010MSCs secreted more BMP\u20102 but less Noggin, accompanied by an overactivation of Smad1\/5\/8 and ERK\u20101\/2. When the Noggin concentration was increased or BMP\u20102 expression was inhibited, the abnormal osteogenic differentiation of AS\u2010MSCs was rectified. In addition, the balance between BMP\u20102 and Noggin secretion was restored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results of this study demonstrate that an imbalance between BMP\u20102 and Noggin secretion induces abnormal osteogenic differentiation of AS\u2010MSCs. These findings reveal a mechanism of pathologic osteogenesis in AS and provide a new perspective on inhibiting pathologic osteogenesis by regulating the balance between BMP\u20102 and Noggin.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39433","type":"journal-article","created":{"date-parts":[[2015,9,28]],"date-time":"2015-09-28T12:48:22Z","timestamp":1443444502000},"page":"430-440","source":"Crossref","is-referenced-by-count":102,"title":["Imbalance Between Bone Morphogenetic Protein 2 and Noggin Induces Abnormal Osteogenic Differentiation of Mesenchymal Stem Cells in Ankylosing Spondylitis"],"prefix":"10.1002","volume":"68","author":[{"given":"Zhongyu","family":"Xie","sequence":"first","affiliation":[{"name":"Sun Yat\u2010sen Memorial Hospital and Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen Memorial Hospital and Sun Yat\u2010sen 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