Synovial joint morphogenesis requires the chondrogenic action of Sox5 and Sox6 in growth plate and articular cartilage

被引：59
作者：
Dy, Peter [1 ,2 ]
Smits, Patrick [1 ,2 ]
Silvester, Amber [1 ,2 ]
Penzo-Mendez, Alfredo [1 ,2 ]
Dumitriu, Bogdan [1 ,2 ]
Han, Yu [1 ,2 ]
de la Motte, Carol A. [3 ]
Kingsley, David M. [4 ,5 ]
Lefebvre, Veronique [1 ,2 ]
机构：
[1] Cleveland Clin, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44195 USA
[2] Cleveland Clin, Lerner Res Inst, Orthopaed & Rheumatol Res Ctr, Cleveland, OH 44195 USA
[3] Cleveland Clin, Lerner Res Inst, Dept Pathobiol, Cleveland, OH 44195 USA
[4] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA
[5] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA
来源：
DEVELOPMENTAL BIOLOGY | 2010年 / 341卷 / 02期
关键词：
Articular cartilage; Development; Differentiation; Erg; Growth plate; Sox5; Sox6; Sox9; Synovial joint; Transcription factor; CRE RECOMBINASE; MOUSE LIMB; GENETIC-ANALYSIS; II COLLAGEN; EXPRESSION; DIFFERENTIATION; TRANSCRIPTION; MUSCLE; TENDON; CELLS;
D O I：
10.1016/j.ydbio.2010.02.024
中图分类号：
Q [生物科学];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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 Sox56 joint morphogenesis block. Sox5/6 inactivation in specified joint cells and chondrocytes (Sox5(fl/fl)6(fl/fl)Col2Cre) also results in a joint morphogenesis block, whereas Sox5/6 inactivation in specified joint cells only (Sox5(fl/fl)6(fl/fl)Gdf5Cre) results in milder joint defects and normal growth plates. Sox5(fl/fl)6(fl/fl)Gdf5Cre 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. (C) 2010 Elsevier Inc. All rights reserved.
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收藏
页码：346 / 359
页数：14
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