{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T10:18:05Z","timestamp":1778840285073,"version":"3.51.4"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2014,8,21]],"date-time":"2014-08-21T00:00:00Z","timestamp":1408579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Studies have shown that mutations in the matrilin-3 gene (MATN3) are associated with multiple epiphyseal dysplasia (MED) and spondyloepimetaphyseal dysplasia (SEMD). We tested whether MATN3 mutations affect the differentiation of chondroprogenitor and\/or mesenchymal stem cells, which are precursors to chondrocytes. ATDC5 chondroprogenitors stably expressing wild-type (WT) MATN3 underwent spontaneous chondrogenesis. Expression of chondrogenic markers collagen II and aggrecan was inhibited in chondroprogenitors carrying the MED or SEMD MATN3 mutations. Hypertrophic marker collagen X remained attenuated in WT MATN3 chondroprogenitors, whereas its expression was elevated in chondroprogenitors expressing the MED or SEMD mutant MATN3 gene suggesting that these mutations inhibit chondrogenesis but promote hypertrophy. TGF-\u03b2 treatment failed to rescue chondrogenesis markers but dramatically increased collagen X mRNA expression in mutant MATN3 expressing chondroprogenitors. Synovium derived mesenchymal stem cells harboring the SEMD mutation exhibited lower glycosaminoglycan content than those of WT MATN3 in response to TGF-\u03b2. Our results suggest that the properties of progenitor cells  harboring MATN3 chondrodysplasia mutations were altered, as evidenced by attenuated chondrogenesis and premature hypertrophy. TGF-\u03b2 treatment failed to completely rescue chondrogenesis but instead induced hypertrophy in mutant MATN3 chondroprogenitors. Our data suggest that chondroprogenitor cells should be considered as a potential target of chondrodysplasia therapy.<\/jats:p>","DOI":"10.3390\/ijms150814555","type":"journal-article","created":{"date-parts":[[2014,8,21]],"date-time":"2014-08-21T11:00:23Z","timestamp":1408618823000},"page":"14555-14573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Matrilin-3 Chondrodysplasia Mutations Cause Attenuated Chondrogenesis, Premature Hypertrophy and Aberrant Response to TGF-\u03b2 in Chondroprogenitor Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2705-0679","authenticated-orcid":false,"given":"Chathuraka","family":"Jayasuriya","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Warren Alpert Medical School of Brown University, CORO West, Suite 402A, 1 Hoppin Street, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Warren Alpert Medical School of Brown University, CORO West, Suite 402A, 1 Hoppin Street, Providence, RI 02903, USA"},{"name":"Sansom Institute of Health Research, Department of Pharmacy and Medical Sciences,  University of South Australia, Adelaide 5000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Pei","sequence":"additional","affiliation":[{"name":"Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics,  West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengke","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Warren Alpert Medical School of Brown University, CORO West, Suite 402A, 1 Hoppin Street, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Lemme","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Warren Alpert Medical School of Brown University, CORO West, Suite 402A, 1 Hoppin Street, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Haines","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Warren Alpert Medical School of Brown University, CORO West, Suite 402A, 1 Hoppin Street, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Warren Alpert Medical School of Brown University, CORO West, Suite 402A, 1 Hoppin Street, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/ng573","article-title":"Mutations in the Region Encoding the Von Willebrand Factor A Domain of Matrilin-3 Are Associated with Multiple Epiphyseal Dysplasia","volume":"28","author":"Chapman","year":"2001","journal-title":"Nat. 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