{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:44:34Z","timestamp":1791330274339,"version":"4.3.1"},"reference-count":64,"publisher":"The Company of Biologists","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,6,15]]},"abstract":"<jats:p>Osteoarthritis primarily affects the articular cartilage of synovial joints. Cell and\/or cartilage replacement is a promising therapy, provided there is access to appropriate tissue and sufficient numbers of articular chondrocytes. Embryonic stem cells (ESCs) represent a potentially unlimited source of chondrocytes and tissues as they can generate a broad spectrum of cell types under appropriate conditions in vitro. Here, we demonstrate that mouse ESC-derived chondrogenic mesoderm arises from a Flk-1\u2212\/Pdgfr\u03b1+ (F\u2212P+) population that emerges in a defined temporal pattern following the development of an early cardiogenic F\u2212P+ population. Specification of the late-arising F\u2212P+ population with BMP4 generated a highly enriched population of chondrocytes expressing genes associated with growth plate hypertrophic chondrocytes. By contrast, specification with Gdf5, together with inhibition of hedgehog and BMP signaling pathways, generated a population of non-hypertrophic chondrocytes that displayed properties of articular chondrocytes. The two chondrocyte populations retained their hypertrophic and non-hypertrophic properties when induced to generate spatially organized proteoglycan-rich cartilage-like tissue in vitro. Transplantation of either type of chondrocyte, or tissue generated from them, into immunodeficient recipients resulted in the development of cartilage tissue and bone within an 8-week period. Significant ossification was not observed when the tissue was transplanted into osteoblast-depleted mice or into diffusion chambers that prevent vascularization. Thus, through stage-specific manipulation of appropriate signaling pathways it is possible to efficiently and reproducibly derive hypertrophic and non-hypertrophic chondrocyte populations from mouse ESCs that are able to generate distinct cartilage-like tissue in vitro and maintain a cartilage tissue phenotype within an avascular and\/or osteoblast-free niche in vivo.<\/jats:p>","DOI":"10.1242\/dev.087890","type":"journal-article","created":{"date-parts":[[2013,5,28]],"date-time":"2013-05-28T20:14:02Z","timestamp":1369772042000},"page":"2597-2610","source":"Crossref","is-referenced-by-count":112,"title":["Specification of chondrocytes and cartilage tissues from embryonic stem cells"],"prefix":"10.1242","volume":"140","author":[{"given":"April M.","family":"Craft","sequence":"first","affiliation":[{"name":"McEwen Centre for Regenerative Medicine, University Health Network, Toronto, ON, M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazish","family":"Ahmed","sequence":"additional","affiliation":[{"name":"CIHR-BioEngineering of Skeletal Tissues Team, Mount Sinai Hospital, University of Toronto, ON, M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S.","family":"Rockel","sequence":"additional","affiliation":[{"name":"Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurpreet S.","family":"Baht","sequence":"additional","affiliation":[{"name":"Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A.","family":"Alman","sequence":"additional","affiliation":[{"name":"Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita A.","family":"Kandel","sequence":"additional","affiliation":[{"name":"CIHR-BioEngineering of Skeletal Tissues Team, Mount Sinai Hospital, University of Toronto, ON, M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agamemnon E.","family":"Grigoriadis","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Development and Stem Cell Biology, Guy's Hospital, King's College London, London, SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon M.","family":"Keller","sequence":"additional","affiliation":[{"name":"McEwen Centre for Regenerative Medicine, University Health Network, Toronto, ON, M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042607192161000_R1","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1089\/ten.tea.2008.0004","article-title":"Cartilage tissue formation using redifferentiated passaged chondrocytes in vitro","volume":"15","author":"Ahmed","year":"2009","journal-title":"Tissue Eng. 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