Dev108530 385..393
نویسندگان
چکیده
The terminal differentiation of hypertrophic chondrocytes is a tightly regulated process that plays a pivotal role in endochondral ossification. As a negative regulator, Sox9 is essentially downregulated in terminally differentiated hypertrophic chondrocytes. However, the underlying mechanism of Sox9 silencing is undefined. Here we show that the zinc finger protein Zbtb20 regulates the terminal differentiation of hypertrophic chondrocytes by repressing Sox9. In the developing skeleton of the mouse, Zbtb20 protein is highly expressed by hypertrophic chondrocytes from late embryonic stages. To determine its physiological role in endochondral ossification, we have generated chondrocyte-specific Zbtb20 knockout mice and demonstrate that disruption of Zbtb20 in chondrocytes results in delayed endochondral ossification and postnatal growth retardation. Zbtb20 deficiency caused a delay in cartilage vascularization and an expansion of the hypertrophic zone owing to reduced expression of Vegfa in the hypertrophic zone. Interestingly, Sox9, a direct suppressor of Vegfa expression, was ectopically upregulated at both mRNA and protein levels in the late Zbtb20-deficient hypertrophic zone. Furthermore, knockdown of Sox9 greatly increased Vegfa expression in Zbtb20-deficient hypertrophic chondrocytes. Our findings point to Zbtb20 as a crucial regulator governing the terminal differentiation of hypertrophic chondrocytes at least partially through repression of Sox9.
منابع مشابه
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Au tor za ko res pon den ci ju/Corresponding aut hor: Josip Božić, General Hospital Varaždin, Department of Anesthesiology reanimation and intensive healing, Ivana Meštrović bb, 42000 Varaždin, Croatia • Tel: +385-42-393 o39 • Fax:+385-42-393 041 • Mob: +385-91-48 67 121 • E-mail: [email protected]; [email protected] Received March 17th 2013; Accepted January 24th 2014; Epiduralna ana...
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