{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:09:45Z","timestamp":1790813385869,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,4,29]],"date-time":"2009-04-29T00:00:00Z","timestamp":1240963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The control of angiogenesis during chondrogenic differentiation is an important issue affecting the use of stem cells in cartilage repair, especially with regard to the persistence of regenerated cartilage. This study was undertaken to investigate the effect of vascular endothelial growth factor (VEGF) stimulation and the blocking of VEGF with its antagonist, soluble Flt\u20101 (sFlt\u20101), on the chondrogenesis of skeletal muscle\u2010derived stem cells (MDSCs) in a rat model of osteoarthritis (OA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the effect of VEGF on cartilage repair in an immunodeficiency rat model of OA after intraarticular injection of murine MDSCs expressing bone morphogenetic protein 4 (BMP\u20104) in combination with MDSCs expressing VEGF or sFlt\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vivo, a combination of sFlt\u20101\u2013 and BMP\u20104\u2013transduced MDSCs demonstrated better repair without osteophyte formation macroscopically and histologically following OA induction, when compared with the other groups. Higher differentiation\/proliferation and lower levels of chondrocyte apoptosis were also observed in sFlt\u20101\u2013 and BMP\u20104\u2013transduced MDSCs compared with a combination of VEGF\u2010 and BMP\u20104\u2013transduced MDSCs or with BMP\u20104\u2013transduced MDSCs alone. In vitro experiments with mixed pellet coculture of MDSCs and OA chondrocytes revealed that BMP\u20104\u2013transduced MDSCs produced the largest pellets, which had the highest gene expression of not only type II collagen and SOX9 but also type X collagen, suggesting formation of hypertrophic chondrocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that MDSC\u2010based therapy involving sFlt\u20101 and BMP\u20104 repairs articular cartilage in OA mainly by having a beneficial effect on chondrogenesis by the donor and host cells as well as by preventing angiogenesis, which eventually prevents cartilage resorption, resulting in persistent cartilage regeneration and repair.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.24443","type":"journal-article","created":{"date-parts":[[2009,4,29]],"date-time":"2009-04-29T10:52:59Z","timestamp":1241002379000},"page":"1390-1405","source":"Crossref","is-referenced-by-count":172,"title":["Cartilage repair in a rat model of osteoarthritis through intraarticular transplantation of muscle\u2010derived stem cells expressing bone morphogenetic protein 4 and soluble flt\u20101"],"prefix":"10.1002","volume":"60","author":[{"given":"Tomoyuki","family":"Matsumoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory M.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burhan","family":"Gharaibeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura 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