{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T22:25:12Z","timestamp":1777933512655,"version":"3.51.4"},"reference-count":67,"publisher":"SAGE Publications","issue":"13","license":[{"start":{"date-parts":[[2014,2,21]],"date-time":"2014-02-21T00:00:00Z","timestamp":1392940800000},"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":["Stem Cells and Development"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:p>\n                    Skeletal dysplasias (SDs) are caused by abnormal chondrogenesis during cartilage growth plate differentiation. To study early stages of aberrant cartilage formation in vitro, we generated the first induced pluripotent stem cells (iPSCs) from fibroblasts of an SD patient with a lethal form of metatropic dysplasia, caused by a dominant mutation (I604M) in the calcium channel gene\n                    <jats:italic toggle=\"yes\">TRPV4<\/jats:italic>\n                    . When micromasses were grown in chondrogenic differentiation conditions and compared with control iPSCs, mutant\n                    <jats:italic toggle=\"yes\">TRPV4<\/jats:italic>\n                    -iPSCs showed significantly (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.05) decreased expression by quantitative real-time polymerase chain reaction of\n                    <jats:italic toggle=\"yes\">COL2A1<\/jats:italic>\n                    (IIA and IIB forms),\n                    <jats:italic toggle=\"yes\">SOX9<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Aggrecan<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">COL10A1<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">RUNX2<\/jats:italic>\n                    , all of which are cartilage growth plate markers. We found that stimulation with\n                    <jats:italic toggle=\"yes\">BMP2<\/jats:italic>\n                    , but not\n                    <jats:italic toggle=\"yes\">TGF\u03b21<\/jats:italic>\n                    , up-regulated\n                    <jats:italic toggle=\"yes\">COL2A1<\/jats:italic>\n                    (IIA and IIB) and\n                    <jats:italic toggle=\"yes\">SOX9<\/jats:italic>\n                    gene expression, only in control iPSCs.\n                    <jats:italic toggle=\"yes\">COL2A1<\/jats:italic>\n                    (Collagen II) expression data were confirmed at the protein level by western blot and immunofluorescence microscopy.\n                    <jats:italic toggle=\"yes\">TRPV4<\/jats:italic>\n                    -iPSCs showed only focal areas of Alcian blue stain for proteoglycans, while in control iPSCs the stain was seen throughout the micromass sample. Similar staining patterns were found in neonatal cartilage from control and patient samples. We also found that\n                    <jats:italic toggle=\"yes\">COL1A1<\/jats:italic>\n                    (Collagen I), a marker of osteogenic differentiation, was significantly (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.05) up-regulated at the mRNA level in\n                    <jats:italic toggle=\"yes\">TRPV4<\/jats:italic>\n                    -iPSCs when compared with the control, and confirmed at the protein level. Collagen I expression in the\n                    <jats:italic toggle=\"yes\">TRPV4<\/jats:italic>\n                    model also may correlate with abnormal staining patterns seen in patient tissues. This study demonstrates that an iPSC model can recapitulate normal chondrogenesis and that mutant\n                    <jats:italic toggle=\"yes\">TRPV4<\/jats:italic>\n                    -iPSCs reflect molecular evidence of aberrant chondrogenic developmental processes, which could be used to design therapeutic approaches for disorders of cartilage.\n                  <\/jats:p>","DOI":"10.1089\/scd.2014.0014","type":"journal-article","created":{"date-parts":[[2014,2,21]],"date-time":"2014-02-21T20:32:28Z","timestamp":1393014748000},"page":"1464-1478","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":47,"title":["Patient-Derived Skeletal Dysplasia Induced Pluripotent Stem Cells Display Abnormal Chondrogenic Marker Expression and Regulation by\n                    <i>BMP2<\/i>\n                    and\n                    <i>TGF\u03b21<\/i>"],"prefix":"10.1177","volume":"23","author":[{"given":"Biagio","family":"Saitta","sequence":"first","affiliation":[{"name":"Cedars-Sinai Medical Center"},{"name":"Medical Genetics Institute"},{"name":"Regenerative Medicine Institute of Cedars-Sinai Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenna","family":"Passarini","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center"},{"name":"Medical Genetics Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhruv","family":"Sareen","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center"},{"name":"Regenerative Medicine Institute of Cedars-Sinai Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loren","family":"Ornelas","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Institute of Cedars-Sinai Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anais","family":"Sahabian","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Institute of Cedars-Sinai Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilpa","family":"Argade","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center"},{"name":"Medical Genetics Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Krakow","sequence":"additional","affiliation":[{"name":"University of California Los Angeles"},{"name":"University of California Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel H.","family":"Cohn","sequence":"additional","affiliation":[{"name":"University of California Los Angeles"},{"name":"University of California Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clive 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