CCN family 2/connective tissue growth factor modulates BMP signalling as a signal conductor, which action regulates the proliferation and differentiation of chondrocytes.
CCN family 2/connective tissue growth factor modulates BMP signalling as a signal conductor, which action regulates the proliferation and differentiation of chondrocytes.
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DOI：
10.1093/jb/mvn159
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发表时间：
2009-02
影响因子：
2.7
通讯作者：
Takigawa M
中科院分区：
文献类型：
--
作者：
Maeda A;Nishida T;Aoyama E;Kubota S;Lyons KM;Kuboki T;Takigawa M
CCN家族2/结缔组织生长因子(CCN2/CTGF)和骨形态发生蛋白(BMP)-2在软骨代谢中发挥重要作用。我们评估了CCN2是否会与BMP-2相互作用，并检查了CCN2与BMP-2（CCN2-BMP-2）的联合作用对软骨细胞的增殖和分化的影响。免疫沉淀-蛋白质印迹分析、固相结合测定和表面等离子共振（SPR）光谱表明，CCN2 直接与 BMP-2 相互作用，SPR 评估解离常数为 0.77 nM。一项体内研究表明，CCN2 与 BMP-2 共定位于 E18.5 小鼠生长板的肥大前区域。有趣的是，CCN2-BMP-2不影响BMP-2/CCN2诱导的p38 MAPK磷酸化，但在培养的软骨细胞中引起ERK1/2磷酸化较少。与这些结果一致，细胞增殖测定表明，CCN2-BMP-2刺激细胞生长的程度比单独使用CCN2或BMP-2要小，而在培养的软骨细胞中，软骨细胞标记基因的表达和代表成熟软骨细胞表型的蛋白聚糖合成通过CCN2-BMP-2处理而协同增加。这些发现表明CCN2可能通过与BMP-2形成复合物作为BMP信号传导的新型调节剂来调节软骨细胞的增殖和分化。
Both CCN family 2/connective tissue growth factor (CCN2/CTGF) and bone morphogenetic protein (BMP)-2 play an important role in cartilage metabolism. We evaluated whether or not CCN2 would interact with BMP-2, and examined the combination effect of CCN2 with BMP-2 (CCN2-BMP-2) on the proliferation and differentiation of chondrocytes. Immunoprecipitation-western blotting analysis, solid-phase binding assay and surface plasmon resonance (SPR) spectroscopy showed that CCN2 directly interacted with BMP-2 with a dissociation constant of 0.77 nM as evaluated by SPR. An in vivo study revealed that CCN2 was co-localized with BMP-2 at the pre-hypertrophic region in the E18.5 mouse growth plate. Interestingly, CCN2-BMP-2 did not affect the BMP-2/CCN2-induced phosphorylation of p38 MAPK but caused less phosphorylation of ERK1/2 in cultured chondrocytes. Consistent with these results, cell proliferation assay showed that CCN2-BMP-2 stimulated cell growth to a lesser degree than by either CCN2 or BMP-2 alone, whereas the expression of chondrocyte marker genes and proteoglycan synthesis, representing the mature chondrocytic phenotype, was increased collaboratively by CCN2-BMP-2 treatment in cultured chondrocytes. These findings suggest that CCN2 may regulate the proliferating and differentiation of chondrocytes by forming a complex with BMP-2 as a novel modulator of BMP signalling.
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影响因子：
4.8
作者：
Inoki, I;Shiomi, T;Okada, Y
通讯作者：
Okada, Y
影响因子：
6.2
作者：
Nishida, T;Kubota, S;Takigawa, M
通讯作者：
Takigawa, M
DOI：
10.1006/bbrc.1998.8895
发表时间：
1998-06-29
影响因子：
3.1
作者：
Nishida, T;Nakanishi, T;Takigawa, M
通讯作者：
Takigawa, M
影响因子：
4.6
作者：
Ivkovic, S;Yoon, BS;Lyons, KM
通讯作者：
Lyons, KM
影响因子：
4
作者：
Inkson, Colette A.;Ono, Mitsuaki;Kuznetsov, Sergei A.;Fisher, Larry W.;Robey, Pamela Gehron;Young, Marian F.
通讯作者：
Young, Marian F.