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Heparin inhibits BMP‐2 osteogenic bioactivity by binding to both BMP‐2 and BMP receptor
Author(s) -
Kanzaki Shin,
Takahashi Tetsu,
Kanno Takahiro,
Ariyoshi Wataru,
Shinmyouzu Kouhei,
Tujisawa Toshiyuki,
Nishihara Tatsuji
Publication year - 2008
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.21468
Subject(s) - osteocalcin , heparin , chemistry , bone morphogenetic protein 2 , bone morphogenetic protein , microbiology and biotechnology , alkaline phosphatase , in vitro , mapk/erk pathway , runx2 , bone morphogenetic protein 7 , osteoblast , receptor , phosphorylation , biochemistry , biology , enzyme , gene
Heparin demonstrates several kinds of biological activities by binding to various extracellular molecules and plays pivotal roles in bone metabolism. However, the role of heparin in the biological activity of bone morphogenetic protein (BMP) remains unclear. In the present study, we examined whether heparin has the effects on osteoblast differentiation induced by BMP‐2 in vitro and also elucidated the precise mechanism by which heparin regulates bone metabolism induced by this molecule. Our results showed that heparin inhibited alkaline phosphatase (ALP) activity and mineralization in osteoblastic cells cultured with BMP‐2. Heparin was found to suppress the mRNA expressions of osterix, Runx2, ALP and osteocalcin, as well as phosphorylation of Smad1/5/8 and p38 MAPK. Further, heparin bound to both BMP‐2 and BMP receptor (BMPR). These results suggest that heparin suppresses BMP‐2‐BMPR binding, and inhibits BMP‐2 osteogenic activity in vitro. J. Cell. Physiol. 216: 844–850, 2008, © 2008 Wiley‐Liss, Inc.