Synovial joint morphogenesis requires the chondrogenic action of Sox5 and Sox6 in growth plate and articular cartilage.
Synovial joint morphogenesis requires the chondrogenic action of Sox5 and Sox6 in growth plate and articular cartilage.
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DOI：
10.1016/j.ydbio.2010.02.024
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发表时间：
2010-05-15
影响因子：
2.7
通讯作者：
Lefebvre V
中科院分区：
文献类型：
--
作者：
Dy P;Smits P;Silvester A;Penzo-Méndez A;Dumitriu B;Han Y;de la Motte CA;Kingsley DM;Lefebvre V
滑膜关节发育的机制仍然知之甚少。在这里，我们使用完整的和细胞特异性的基因失活，以确定多余的软骨形成转录因子Sox 5和Sox 6在这一过程中的作用。我们发现，在完全突变体（Sox 5 −/−6−/−）中，联合发育早期中止。Gdf 5和Wnt 9a在关节前体细胞中的表达是准时的，但Sox 9下调和关节间带的细胞凝聚是晚期的。关节细胞分化是不成功的，无论血统，和空化失败。野生型胚胎中Sox 5和Sox 6的表达局限于软骨细胞，Sox 5 −/−6−/−生长板中Erg的持续表达和Ihh的弱表达表明，生长板失效导致了Sox 5 −/−6−/−关节形态发生阻滞。在特定关节细胞和软骨细胞中的Sox 5/6失活（Sox 5 fl/fl 6 fl/flCol 2Cre）也导致关节形态发生阻滞，而仅在特定关节细胞中的Sox 5/6失活（Sox 5 fl/fl 6 fl/flGdf 5Cre）导致较轻微的关节缺陷和正常的生长板。Sox 5 fl/fl 6 fl/flGdf 5Cre关节软骨细胞保持未分化，如持续的Gdf 5表达和泛软骨基因下调所示。沿着Prg 4下调，这些缺陷可能是成年小鼠关节组织过度生长和不完全空化的原因。总之，这些数据表明，滑膜关节形态发生依赖于Sox 5/6在促进生长板和关节软骨细胞分化中的重要作用。
The mechanisms underlying synovial joint development remain poorly understood. Here we use complete and cell-specific gene inactivation to identify the roles of the redundant chondrogenic transcription factors Sox5 and Sox6 in this process. We show that joint development aborts early in complete mutants (Sox5−/−6−/−). Gdf5 and Wnt9a expression is punctual in articular progenitor cells, but Sox9 downregulation and cell condensation in joint interzones are late. Joint cell differentiation is unsuccessful, regardless of lineage, and cavitation fails. Sox5 and Sox6 restricted expression to chondrocytes in wild-type embryos and continued Erg expression and weak Ihh expression in Sox5−/−6−/− growth plates suggest that growth plate failure contribute to this Sox5−/−6−/− joint morphogenesis block. Sox5/6 inactivation in specified joint cells and chondrocytes (Sox5fl/fl6fl/flCol2Cre) also results in a joint morphogenesis block, whereas Sox5/6 inactivation in specified joint cells only (Sox5fl/fl6fl/flGdf5Cre) results in milder joint defects and normal growth plates. Sox5fl/fl6fl/flGdf5Cre articular chondrocytes remain undifferentiated, as shown by continued Gdf5 expression and pancartilaginous gene downregulation. Along with Prg4 downregulation, these defects likely account for joint tissue overgrowth and incomplete cavitation in adult mice. Together, these data suggest that synovial joint morphogenesis relies on essential roles for Sox5/6 in promoting both growth plate and articular chondrocyte differentiation.
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影响因子：
2.4
作者：
Ito, MM;Kida, MY
通讯作者：
Kida, MY
影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
DOI：
10.1002/bdrc.20005
发表时间：
2004-03-01
期刊：
Birth defects research. Part C, Embryo today : reviews
影响因子：
--
作者：
Kirn-Safran, Catherine B;Gomes, Ronald R;Carson, Daniel D
通讯作者：
Carson, Daniel D
影响因子：
5.3
作者：
Han, Yu;Lefebvre, Veronique
通讯作者：
Lefebvre, Veronique
影响因子：
2.6
作者：
DHORDAIN, P;DEWITTE, F;DUTERQUECOQUILLAUD, M
通讯作者：
DUTERQUECOQUILLAUD, M