TGF-beta1 and WISP-1/CCN-4 can regulate each other's activity to cooperatively control osteoblast function.
TGF-beta1 and WISP-1/CCN-4 can regulate each other's activity to cooperatively control osteoblast function.
复制标题
DOI：
10.1002/jcb.21754
复制
发表时间：
2008-08-01
影响因子：
4
通讯作者：
Young, Marian F.
中科院分区：
文献类型：
--
作者：
Inkson, Colette A.;Ono, Mitsuaki;Kuznetsov, Sergei A.;Fisher, Larry W.;Robey, Pamela Gehron;Young, Marian F.
Wnt诱导分泌蛋白 - 1（WISP - 1）与CCN家族的其他成员一样，在骨骼组织中表达。其作用机制仍不清楚。通过逆转录聚合酶链反应（RT - PCR）分析了人骨髓基质细胞（BMSC）中WISP - 1的表达。我们鉴定出两种主要的转录本，分别对应全长WISP - 1以及缺失一个假定的骨形态发生蛋白/转化生长因子 - β（BMP/TGF - β）结合位点的剪接变体WISP - 1va。为了研究WISP - 1在骨骼中的功能，用重组人（rh）WISP - 1处理骨髓基质细胞培养物，并分析其增殖和成骨分化情况。WISP - 1处理增加了5 - 溴脱氧尿嘧啶核苷（BrdU）的掺入以及碱性磷酸酶（AP）的活性。考虑到已知的转化生长因子 - β超家族与CCN家族成员之间存在功能协同作用，我们接下来测试了WISP - 1对转化生长因子 - β1活性的影响。我们发现重组人WISP - 1能够减少重组人转化生长因子 - β1诱导的BrdU掺入。同样，重组人转化生长因子 - β1抑制了重组人WISP - 1对碱性磷酸酶活性的诱导。为了探究WISP - 1变体之间的功能差异，将WISP - 1或WISP - 1va转染到骨髓基质细胞中。两种变体都能强烈诱导BrdU掺入。然而，在没有额外的成骨刺激（如转化生长因子 - β1）的情况下，两种变体对碱性磷酸酶活性都没有影响。综合我们的结果表明WISP - 1和转化生长因子 - β1之间存在功能关系。为了进一步明确这种关系，我们分析了WISP - 1对转化生长因子 - β信号传导的影响。重组人WISP - 1显著降低了转化生长因子 - β1诱导的Smad - 2磷酸化。我们的数据表明全长WISP - 1及其变体WISP - 1va是增殖和成骨分化的调节因子，并且可能是成骨细胞样细胞中转化生长因子 - β1信号传导的新型调节因子。
Wnt-induced secreted protein – 1 (WISP-1), like other members of the CCN family, is expressed in skeletal tissues. Its mechanism of action remains unknown. Expression of WISP-1 was analyzed in human bone marrow stroma cells (BMSC) by RT-PCR. We identified two major transcripts corresponding to those of full length WISP-1, and of the splice variant WISP-1va which lacks a putative BMP/TGF-β binding site. To investigate the function of WISP-1 in bone, BMSC cultures were treated with recombinant human (rh)WISP-1 and analyzed for proliferation and osteogenic differentiation. WISP-1 treatment increased both BrdU incorporation and alkaline phosphatase (AP) activity. Considering the known functional synergy found between the TGF-β super-family and members of the CCN family, we next tested the effect of WISP-1 on TGF-β1 activity. We found that rhWISP-1 could reduce rhTGF-β1 induced BrdU incorporation. Similarly, rhTGF-β1 inhibited rhWISP-1 induction of AP activity. To explore functional differences between the WISP-1 variants, WISP-1 or WISP-1va were transfected into BMSC. Both variants could strongly induce BrdU incorporation. However, there were no effects of either variant on AP activity without an additional osteogenic stimulus such as TGF-β1. Taken together our results suggest a functional relationship between WISP-1 and TGF-β1. To further define this relationship we analyzed the effect of WISP-1 on TGF-β signaling. rhWISP-1 significantly reduced TGF-β1 induced phosphorylation of smad-2. Our data indicates that full length WISP-1 and its variant WISP-1va are modulators of proliferation and osteogenic differentiation, and may be a novel regulators of TGF-β1 signaling in osteoblast-like cells.
登录
查看更多内容
影响因子：
4.8
作者：
Luo, Q;Kang, Q;He, TC
通讯作者：
He, TC
DOI：
10.1073/pnas.94.24.12981
发表时间：
1997-11-25
影响因子：
11.1
作者：
Kim, HS;Nagalla, SR;Rosenfeld, RG
通讯作者：
Rosenfeld, RG
DOI：
10.1016/s0006-291x(02)00700-3
发表时间：
2002-07-12
影响因子：
3.1
作者：
Eguchi, T;Kubota, S;Takigawa, M
通讯作者：
Takigawa, M
影响因子：
4.8
作者：
Chen, CC;Chen, NY;Lau, LF
通讯作者：
Lau, LF
影响因子：
4.8
作者：
Leu, SJ;Lam, SCT;Lau, LF
通讯作者：
Lau, LF