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- Title
Heparin inhibits BMP-2 osteogenic bioactivity by binding to both BMP-2 and BMP receptor.
- Authors
Kanzaki, Shin; Takahashi, Tetsu; Kanno, Takahiro; Ariyoshi, Wataru; Shinmyouzu, Kouhei; Tujisawa, Toshiyuki; Nishihara, Tatsuji
- Abstract
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.
- Subjects
HEPARIN; BONE metabolism; BONE morphogenetic proteins; ALKALINE phosphatase; MESSENGER RNA; PHOSPHORYLATION
- Publication
Journal of Cellular Physiology, 2008, Vol 216, Issue 3, p844
- ISSN
0021-9541
- Publication type
Article
- DOI
10.1002/jcp.21468