共查询到20条相似文献,搜索用时 109 毫秒
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Katarzyna A. Dudek Jér?me E. Lafont Aida Martinez-Sanchez Christopher L. Murphy 《The Journal of biological chemistry》2010,285(32):24381-24387
miRNAs have been shown to be essential for normal cartilage development in the mouse. However, the role of specific miRNAs in cartilage function is unknown. Using rarely available healthy human chondrocytes (obtained from 8 to 50 year old patients), we detected a most highly abundant primary miRNA H19, whose expression was heavily dependent on cartilage master regulator SOX9. Across a range of murine tissues, expression of both H19- and H19-derived miR-675 mirrored that of cartilage-specific SOX9. miR-675 was shown to up-regulate the essential cartilage matrix component COL2A1, and overexpression of miR-675 rescued COL2A1 levels in H19- or SOX9-depleted cells. We thus provide evidence that SOX9 positively regulates COL2A1 in human articular chondrocytes via a previously unreported miR-675-dependent mechanism. This represents a novel pathway regulating cartilage matrix production and identifies miR-675 as a promising new target for cartilage repair. 相似文献
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Olga Shakhova Phil Cheng Pravin J. Mishra Daniel Zingg Simon M. Schaefer Julien Debbache Jessica H?usel Claudia Matter Theresa Guo Sean Davis Paul Meltzer Daniela Mihic-Probst Holger Moch Michael Wegner Glenn Merlino Mitchell P. Levesque Reinhard Dummer Raffaella Santoro Paolo Cinelli Lukas Sommer 《PLoS genetics》2015,11(1)
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Dagmar Wilhelm Linda L. Washburn Vy Truong Marc Fellous Eva M. Eicher Peter Koopman 《Mechanisms of development》2009,126(5-6):324-336
Ovotestis development in B6-XYPOS mice provides a rare opportunity to study the interaction of the testis- and ovary-determining pathways in the same tissue. We studied expression of several markers of mouse fetal testis (SRY, SOX9) or ovary (FOXL2, Rspo1) development in B6-XYPOS ovotestes by immunofluorescence, using normal testes and ovaries as controls. In ovotestes, SOX9 was expressed only in the central region where SRY is expressed earliest, resulting in testis cord formation. Surprisingly, FOXL2-expressing cells also were found in this region, but individual cells expressed either FOXL2 or SOX9, not both. At the poles, even though SOX9 was not up-regulated, SRY expression was down-regulated normally as in XY testes, and FOXL2 was expressed from an early stage, demonstrating ovarian differentiation in these areas. Our data (1) show that SRY must act within a specific developmental window to activate Sox9; (2) challenge the established view that SOX9 is responsible for down-regulating Sry expression; (3) disprove the concept that testicular and ovarian cells occupy discrete domains in ovotestes; and (4) suggest that FOXL2 is actively suppressed in Sertoli cell precursors by the action of SOX9. Together these findings provide important new insights into the molecular regulation of testis and ovary development. 相似文献
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