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CCN3 increases BMP‐4 expression and bone mineralization in osteoblasts
Author(s) -
Tan TzuWei,
Huang YuanLin,
Chang JungTzu,
Lin JenJyh,
Fong YiChin,
Kuo ChienChung,
Tsai ChunHao,
Chen YenJen,
Hsu HorngChaung,
Cho DerYang,
Chen YiHung,
Tang ChihHsin
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22991
Subject(s) - osteoblast , chemistry , microbiology and biotechnology , p38 mitogen activated protein kinases , bone morphogenetic protein 2 , phosphorylation , bone morphogenetic protein , bone morphogenetic protein 7 , activator (genetics) , signal transduction , mesenchymal stem cell , integrin , protein kinase a , medicine , receptor , biology , in vitro , gene , biochemistry
The nephroblastoma overexpressed (NOV) gene, also called CCN3, regulates differentiation of skeletal mesenchymal cells. Bone morphogenetic proteins (BMPs) play important roles in osteoblast differentiation and bone formation, but the effects of CCN3 on BMP expression and bone formation in cultured osteoblasts are largely unknown. Here we found that CCN3 increased BMP‐4 expression and bone nodule formation in cultured osteoblast. Monoclonal antibodies for α5β1 and αvβ5 integrins, and inhibitors of integrin‐linked kinase (ILK), p38, and JNK, all inhibited CCN3‐induced bone nodule formation and BMP‐4 up‐regulation of osteoblasts. CCN3 stimulation increased the kinase activity of ILK and phosphorylation of p38 and JNK. Inhibitors of activator protein‐1 (AP‐1) also suppressed bone nodule formation and BMP‐4 expression enhanced by CCN3. Moreover, CCN3‐induced c‐Jun translocation into the nucleus, and the binding of c‐Jun to the AP‐1 element on the BMP‐4 promoter were both inhibited by specific inhibitors of the ILK, p38, and JNK cascades. Taken together, our results provide evidence that CCN3 enhances BMP‐4 expression and bone nodule formation in osteoblasts, and that the integrin receptor, ILK, p38, JNK, and AP‐1 signaling pathways may be involved. J. Cell. Physiol. 227: 2531–2541, 2012. © 2011 Wiley Periodicals, Inc.