Smad6 is induced by BMP-2 and modulates chondrocyte differentiation
Smad6 is induced by BMP-2 and modulates chondrocyte differentiation
复制标题
DOI：
10.1016/s0736-0266(03)00008-1
复制
发表时间：
2003-09-01
影响因子：
2.8
通讯作者：
O'Keefe, RJ
中科院分区：
文献类型：
--
作者：
Li, XF;Ionescu, AM;O'Keefe, RJ
BMP调节软骨分化，并已被批准用于临床作为骨修复的刺激剂。BNIP信号传导是复杂的，并且存在多个潜在的调节点，包括Smad信号传导的调节，其被Smad 6和Smad 7抑制。在本论文中，我们评估了Smad 6在软骨细胞分化过程中的表达和生物学功能。我们发现，诱导软骨细胞分化的BMP-2在鸡胸骨胚胎软骨细胞伴随着Smad 6 mRNA和蛋白水平显着增加。与Smad 6互补的吗啉代反义寡核苷酸降低了Smad 6蛋白的表达，并增强了BMP-2对colX和碱性磷酸酶活性的刺激作用。相反，Smad 6的过表达阻断了BMP-2介导的X型胶原启动子b2-640 Luc的诱导。因此，表达研究以及功能获得和丧失实验表明，Smad 6参与了一个重要的负反馈回路，由此BMP-2介导的对软骨细胞分化的影响通过Smad 6的诱导而降低。需要进一步的研究，以确定在何种程度上这一途径参与病理过程涉及软骨。(C)2003骨科研究学会。由爱思唯尔有限公司出版。保留所有权利。
BMPs regulate cartilage differentiation and have been approved for clinical use as stimulators of bone repair. BNIP signaling is complex and there are multiple potential points of regulation, including modulation of Smad signaling, which is inhibited by both Smad6 and Smad7. In the current manuscript we assessed the expression and biological function of Smad6 during chondrocyte differentiation. We found that the induction of chondrocyte differentiation by BMP-2 in chicken sternal embryonic chondrocytes was accompanied by a marked increase in Smad6 mRNA and protein levels. A morpholino antisense oligonucleotide complementary to Smad6 reduced the expression of Smad6 protein and enhanced the stimulatory effect of BMP-2 on both colX and alkaline phosphatase activity. In contrast, over-expression of Smad6 blocked BMP-2 mediated induction of the type X collagen promoter, b2-640 Luc. Therefore, expression studies as well as gain and loss of function experiments suggest that Smad6 participates in an important negative feedback loop whereby BMP-2 mediated effects on chondrocyte differentiation are reduced by induction of Smad6. Additional studies are required to determine the extent to which this pathway participates in pathologic processes involving cartilage. (C) 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.