CCN family 2/connective tissue growth factor (CCN2/CTGF) promotes osteoclastogenesis via induction of and interaction with dendritic cell-specific transmembrane protein (DC-STAMP).
CCN family 2/connective tissue growth factor (CCN2/CTGF) promotes osteoclastogenesis via induction of and interaction with dendritic cell-specific transmembrane protein (DC-STAMP).
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DOI：
10.1002/jbmr.222
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发表时间：
2011-02
影响因子：
6.2
通讯作者：
Takigawa, Masaharu
中科院分区：
文献类型：
--
作者：
Nishida, Takashi;Emura, Kenji;Kubota, Satoshi;Lyons, Karen M.;Takigawa, Masaharu
关键词：
CCN家族2/结缔组织生长因子（CCN 2/CTGF）促进软骨内骨化。然而，CCN 2在骨替代肥大软骨中的作用仍不清楚。Ccn 2缺失小鼠的表型具有扩大的肥大区，表明其中软骨细胞外基质的再吸收受损。因此，我们分析了CCN 2在破骨细胞生成中的作用，因为软骨细胞外基质在软骨内骨化过程中主要被破骨细胞吸收。用谷胱甘肽S转移酶（GST）融合的小鼠NF-κB配体受体激活剂（GST-RANKL）处理后第6天，小鼠巨噬细胞系RAW 264.7中Ccn 2基因的表达上调，与单独使用GST-RANKL相比，重组CCN 2（rCCN 2）和GST-RANKL的组合显着增强了抗酒石酸酸性磷酸酶（TRACP）阳性多核细胞的形成。因此，我们怀疑CCN 2参与破骨细胞生成过程中的细胞-细胞融合。为了阐明机制，我们进行了实时PCR分析的基因表达，免疫共沉淀分析，CCN 2和树突状细胞特异性跨膜蛋白（DC-STAMP），这是参与细胞-细胞融合的固相结合试验。结果表明，CCN 2对DC-STAMP有诱导作用，并与DC-STAMP相互作用。此外，GST-RANKL诱导的破骨细胞生成在Ccn 2基因敲除小鼠的胎肝细胞中受损，通过添加外源性rCCN 2或通过逆转录病毒载体强制表达DC-STAMP来挽救受损的破骨细胞形成。这些结果表明，在破骨细胞生成过程中表达的CCN 2通过诱导和与DC-STAMP相互作用促进破骨细胞形成。
CCN family 2/connective tissue growth factor (CCN2/CTGF) promotes endochondral ossification. However, the role of CCN2 in the replacement of hypertrophic cartilage with bone is still unclear. The phenotype of Ccn2 null mice, having an expanded hypertrophic zone, indicates that the resorption of the cartilage extracellular matrix is impaired therein. Therefore, we analyzed the role of CCN2 in osteoclastogenesis because cartilage extracellular matrix is resorbed mainly by osteoclasts during endochondral ossification. Expression of the Ccn2 gene was upregulated in mouse macrophage cell line RAW264.7 on day 6 after treatment of glutathione S transferase (GST) fusion mouse receptor activator of NF-κB ligand (GST-RANKL), and a combination of recombinant CCN2 (rCCN2) and GST-RANKL significantly enhanced tartrate-resistant acid phosphatase (TRACP)–positive multinucleated cell formation compared with GST-RANKL alone. Therefore, we suspected the involvement of CCN2 in cell-cell fusion during osteoclastogenesis. To clarify the mechanism, we performed real-time PCR analysis of gene expression, coimmunoprecipitation analysis, and solid-phase binding assay of CCN2 and dendritic cell–specific transmembrane protein (DC-STAMP), which is involved in cell-cell fusion. The results showed that CCN2 induced and interacted with DC-STAMP. Furthermore, GST-RANKL–induced osteoclastogenesis was impaired in fetal liver cells from Ccn2 null mice, and the impaired osteoclast formation was rescued by the addition of exogenous rCCN2 or the forced expression of DC-STAMP by a retroviral vector. These results suggest that CCN2 expressed during osteoclastogenesis promotes osteoclast formation via induction of and interaction with DC-STAMP.
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影响因子：
2.7
作者：
Maeda A;Nishida T;Aoyama E;Kubota S;Lyons KM;Kuboki T;Takigawa M
通讯作者：
Takigawa M
影响因子：
6.2
作者：
Nishida, T;Kubota, S;Takigawa, M
通讯作者：
Takigawa, M
影响因子：
3.5
作者：
Kubota, S;Hattori, T;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