Matrilin-3 chondrodysplasia mutations cause attenuated chondrogenesis, premature hypertrophy and aberrant response to TGF-β in chondroprogenitor cells.
Matrilin-3 chondrodysplasia mutations cause attenuated chondrogenesis, premature hypertrophy and aberrant response to TGF-β in chondroprogenitor cells.
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母素-3软骨增生突变会导致软骨发生，过早肥大和对TGF-β的软骨元素细胞的异常反应。
DOI：
10.3390/ijms150814555
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发表时间：
2014-08-21
影响因子：
5.6
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Jayasuriya CT;Zhou FH;Pei M;Wang Z;Lemme NJ;Haines P;Chen Q
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-β 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-β. Our results suggest that the properties of progenitor cells harboring MATN3 chondrodysplasia mutations were altered, as evidenced by attenuated chondrogenesis and premature hypertrophy. TGF-β 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.
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影响因子：
5.3
作者：
Budde, B;Blumbach, K;Grässel, S
通讯作者：
Grässel, S
影响因子：
3.9
作者：
Cotterill, SL;Jackson, GC;Briggs, MD
通讯作者：
Briggs, MD
影响因子：
4.8
作者：
Mann, HH;Özbek, S;Wagener, R
通讯作者：
Wagener, R
DOI：
10.1016/0922-3371(90)90079-c
发表时间：
1990-05-01
期刊：
CELL DIFFERENTIATION AND DEVELOPMENT
影响因子：
--
作者：
ATSUMI, T;MIWA, Y;IKAWA, Y
通讯作者：
IKAWA, Y
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ