{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T08:22:57Z","timestamp":1782202977621,"version":"3.54.5"},"reference-count":53,"publisher":"SAGE Publications","issue":"17-18","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:p>\n                    Implantation of genetically modified chondrogenically competent human bone marrow-derived mesenchymal stromal cells (hMSCs) is an attractive strategy to improve cartilage repair. The goal of this study was to examine the potential benefits of transferring a sequence coding for the\n                    <jats:italic toggle=\"yes\">bone morphogenetic protein 3<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">BMP-3<\/jats:italic>\n                    ) that modulates bone and cartilage formation, using recombinant adeno-associated virus (rAAV) vectors on the chondroreparative activities of hMSCs. Undifferentiated and chondrogenically induced primary human MSCs were treated with an rAAV-h\n                    <jats:italic toggle=\"yes\">BMP-3<\/jats:italic>\n                    construct to evaluate its effects on the proliferative, metabolic, and chondrogenic activities of the cells compared with control (reporter rAAV-\n                    <jats:italic toggle=\"yes\">lacZ<\/jats:italic>\n                    vector) condition. Effective\n                    <jats:italic toggle=\"yes\">BMP-3<\/jats:italic>\n                    expression was noted both in undifferentiated and chondrogenically differentiated cells in the presence of rAAV-h\n                    <jats:italic toggle=\"yes\">BMP-3<\/jats:italic>\n                    relative to rAAV-\n                    <jats:italic toggle=\"yes\">lacZ<\/jats:italic>\n                    , stimulating cell proliferation and extracellular matrix (proteoglycans, type-II collagen) deposition together with higher levels of chondrogenic\n                    <jats:italic toggle=\"yes\">sex-determining region Y-type high-mobility group box 9<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">SOX9<\/jats:italic>\n                    ) expression. rAAV-h\n                    <jats:italic toggle=\"yes\">BMP-3<\/jats:italic>\n                    also advantageously decreased terminal differentiation, hypertrophy, and osteogenesis (type-I\/-X collagen and alkaline phosphatase expression), with reduced levels of osteoblast-related\n                    <jats:italic toggle=\"yes\">runt-related transcription factor 2<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">RUNX-2<\/jats:italic>\n                    ) transcription factor and\n                    <jats:italic toggle=\"yes\">\u03b2-catenin<\/jats:italic>\n                    (osteodifferentiation mediator) and\n                    <jats:italic toggle=\"yes\">enhanced parathyroid hormone-related protein<\/jats:italic>\n                    expression (inhibitor of hypertrophic maturation, calcification, and bone formation). This study shows the advantage of modifying hMSCs with rAAV-h\n                    <jats:italic toggle=\"yes\">BMP-3<\/jats:italic>\n                    to trigger adapted chondroreparative activities as a source of improved cells for transplantation protocols in cartilage defects.\n                  <\/jats:p>","DOI":"10.1089\/hum.2022.004","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T05:15:19Z","timestamp":1655529319000},"page":"950-958","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of Recombinant Adeno-Associated Virus-Mediated Overexpression of\n                    <i>Bone Morphogenetic Protein 3<\/i>\n                    on the Chondrogenic Fate of Human Bone Marrow-Derived Mesenchymal Stromal Cells"],"prefix":"10.1177","volume":"33","author":[{"given":"Jagadeesh K.","family":"Venkatesan","sequence":"first","affiliation":[{"name":"Center of Experimental Orthopedics, Saarland University and Saarland University Medical Center, Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertrud","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Center of Experimental Orthopedics, Saarland University and Saarland University Medical Center, Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Speicher-Mentges","sequence":"additional","affiliation":[{"name":"Center of Experimental Orthopedics, Saarland University and Saarland University Medical Center, Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Orth","sequence":"additional","affiliation":[{"name":"Center of Experimental Orthopedics, Saarland University and Saarland University Medical Center, Homburg, Germany"},{"name":"Department of Orthopedic Surgery, Saarland University Medical Center, Homburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Madry","sequence":"additional","affiliation":[{"name":"Center of Experimental Orthopedics, Saarland University and Saarland University Medical Center, Homburg, Germany"},{"name":"Department of Orthopedic Surgery, Saarland University Medical Center, Homburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0323-8922","authenticated-orcid":false,"given":"Magali","family":"Cucchiarini","sequence":"additional","affiliation":[{"name":"Center of Experimental Orthopedics, Saarland University and Saarland University Medical Center, Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.2519\/jospt.1998.28.4.192"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199812000-00011"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/joca.2002.0801"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199410063311401"},{"key":"e_1_3_5_6_2","first-page":"669","article-title":"Cartilage repair and joint preservation: medical and surgical treatment options","volume":"108","author":"Madry H","year":"2011","unstructured":"Madry H, , Gr\u00fcn UW, , Knutsen G. Cartilage repair and joint preservation: medical and surgical treatment options. Dtsch Arztebl Int, 2011; 108:669\u2013677.","journal-title":"Dtsch Arztebl Int"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1997.3858"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.1998.4.415"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5411.143"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2003.11.001"},{"key":"e_1_3_5_11_2","first-page":"1","article-title":"Current perspectives in stem cell research for knee cartilage repair","volume":"7","author":"Orth P","year":"2014","unstructured":"Orth P, , Rey-Rico A, , Venkatesan JK, et al. Current perspectives in stem cell research for knee cartilage repair. 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