{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T21:09:57Z","timestamp":1773695397007,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,6,27]],"date-time":"2018-06-27T00:00:00Z","timestamp":1530057600000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR053860"],"award-info":[{"award-number":["R01 AR053860"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["T90DE022736"],"award-info":[{"award-number":["T90DE022736"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Members of the transforming growth factor beta (TGF\u2010\u03b2) family are secreted proteins that regulate skeletal development. TGF\u2010\u03b2 signaling is critical in embryonic development of the annulus fibrosus (AF) of the intervertebral disc (IVD). To address the question of the role of TGF\u2010\u03b2 signaling in postnatal development and maintenance of the skeleton, we generated mice in which <jats:italic>Tgfbr2<\/jats:italic> was deleted at 2\u2010weeks of age in Aggrecan (Acan)\u2010expressing cells using inducible Cre\/LoxP recombination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Localization of Cre recombination was visualized by crossing Acan<jats:sup>tm1(cre\/ERT2)Crm<\/jats:sup> mice to fluorescent mTmG reporter mice. Acan<jats:sup>tm1(cre\/ERT2)Crm<\/jats:sup> mice were mated to <jats:italic>Tgfbr2<\/jats:italic><jats:sup>LoxP\/LoxP<\/jats:sup> mice and Cre recombinase was activated by tamoxifen injection at 2\u2010weeks postnatally. Following tamoxifen injection, mice were aged to 3, 6, and 12\u2010months and control mice were compared to the experimental (cKO) group. Mice were initially analyzed using X\u2010ray and skeletal preparations. Sternocostal joints and IVD tissues were further analyzed histologically by hematoxylin and eosin (H&amp;E), Safranin O, and Picrosirius Red staining as well as Col10 immunostaining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cre recombination was observed in the IVD and sternocostal joints. X\u2010ray analysis revealed osteophyte formation within the disc space of 12\u2010month\u2010old cKO mice. Skeletal preparations confirmed calcification within the IVD and the sternocostal joints in cKO mice. H&amp;E staining of cKO IVD revealed disorganized growth plates, delay in the formation of the bony endplate, and Col10 staining in the AF indicative of ectopic endochondral bone formation. Furthermore, proteoglycan loss was observed and collagen bundles within the inner AF were thinner and less organized. Alterations in the IVD were apparent beginning at 3 months and were progressively more visible at 6 and 12\u2009months. Similarly, histological analysis of cKO sternocostal joints revealed joint calcification, proteoglycan loss, and disorganization of the collagen architecture at 12\u2009months of age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TGF\u2010\u03b2 signaling is important for postnatal development and maintenance of fibrocartilaginous IVD and sternocostal joints.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.1025","type":"journal-article","created":{"date-parts":[[2018,6,23]],"date-time":"2018-06-23T02:09:36Z","timestamp":1529719776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Tgfbr2 is required in Acan\u2010expressing cells for maintenance of the intervertebral and sternocostal joints"],"prefix":"10.1002","volume":"1","author":[{"given":"Bashar","family":"Alkhatib","sequence":"first","affiliation":[{"name":"Department of Cell, Developmental and Integrative Biology University of 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