Distinct functions of BMP4 and GDF5 in the regulation of chondrogenesis
Distinct functions of BMP4 and GDF5 in the regulation of chondrogenesis
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DOI：
10.1002/jcb.20019
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发表时间：
2004-04-15
影响因子：
4
通讯作者：
Shum, L
中科院分区：
文献类型：
--
作者：
Hatakeyama, Y;Tuan, RS;Shum, L
骨形态发生蛋白4(BMP4)和生长分化因子5(GDF5)是密切相关的蛋白质家族成员，调节早期软骨的形态和分化。在这项研究中，我们系统地比较了它们在微团培养中生长的小鼠胚胎肢芽间充质软骨形成的不同阶段的作用结果。总体而言，这两种生长因子都促进了这些培养物中软骨的生长和分化。独特的是，BMP4不仅能促进软骨结节的形成和成熟，还能诱导结节间充质细胞表达软骨分化标志物。另一方面，GDF5增加了软骨形成前间充质细胞凝聚和软骨结节的数量，但没有改变整个分化模式。此外，GDF5导致Sox9的表达水平比与BMP4相关的表达水平更持久地升高。在整个培养过程中，BMP4促进了软骨细胞的成熟，并维持了高水平的COL0表达，而GDF5则导致COL10表达的一过性增加。综上所述，我们得出结论：BMP4对软骨形成有指导作用，并诱导间充质细胞向成软骨方向分化。此外，BMP4加速了软骨分化成熟的进程。GDF5通过促进软骨前体细胞聚集，放大软骨分化标志物的反应，促进软骨形成。这些差异可能有助于微调正常的软骨分化程序，并可用于仿生学的分子操作。J.细胞。生物化学。电话：1204-1217,2004。2004年出版，威利-利斯，lnc。
Bone morphogenetic protein 4 (BMP4) and growth/differentiation factor 5 (GDF5) are closely related protein family members and regulate early cartilage patterning and differentiation. In this study, we compared the functional outcome of their actions systematically at various stages of chondrogenesis in mouse embryonic limb bud mesenchyme grown in micromass cultures. Overall, both growth factors enhanced cartilage growth and differentiation in these cultures. Uniquely, BMP4 not only accelerated the formation and maturation of cartilaginous nodules, but also induced internodular mesenchymal cells to express cartilage differentiation markers. On the other hand, GDF5 increased the number of prechondrogenic mesenchymal cell condensation and cartilaginous nodules, without altering the overall pattern of differentiation. In addition, GDF5 caused a more sustained elevated expression level of Sox9 relative to that associated with BMP4. BMP4 accelerated chondrocyte maturation throughout the cultures and sustained an elevated level of Coll 0 expression, whereas GDF5 caused a transient increase in Col10 expression. Taken together, we conclude that BMP4 is instructive to chondrogenesis and induces mesenchymal cells toward the chondrogenic lineage. Furthermore, BMP4 accelerates the progression of cartilage differentiation to maturation. GDF5 enhances cartilage formation by promoting chondroprogenitor cell aggregation, and amplifying the responses of cartilage differentiation markers. These differences may serve to fine-tune the normal cartilage differentiation program, and can be exploited for the molecular manipulation in biomimetics. J. Cell. Biochem. 91: 1204-1217, 2004. Published 2004 Wiley-Liss, lnc.