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TGF‐β1 and WISP‐1/CCN‐4 can regulate each other's activity to cooperatively control osteoblast function
Author(s) -
Inkson Colette A.,
Ono Mitsuaki,
Kuznetsov Sergei A.,
Fisher Larry W.,
Robey Pamela Gehron,
Young Marian F.
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21754
Subject(s) - smad , wnt signaling pathway , osteoblast , transfection , transforming growth factor , recombinant dna , phosphorylation , chemistry , microbiology and biotechnology , signal transduction , bone morphogenetic protein , biology , cell culture , biochemistry , genetics , in vitro , gene
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 (hBMSC) 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, hBMSC 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 hBMSC. 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 novel regulators of TGF‐β1 signaling in osteoblast‐like cells. J. Cell. Biochem. 104: 1865–1878, 2008. © 2008 Wiley‐Liss, Inc.