Heparin inhibits BMP-2 osteogenic bioactivity by binding to both BMP-2 and BMP receptor

被引：61

作者：

Kanzaki, Shin ^{[1
,2
]}

Takahashi, Tetsu ^{[1
]}

Kanno, Takahiro ^{[1
,3
]}

Ariyoshi, Wataru ^{[1
]}

Shinmyouzu, Kouhei ^{[1
]}

Tujisawa, Toshiyuki ^{[2
]}

Nishihara, Tatsuji ^{[2
]}

机构：

[1] Kyushu Dent Coll, Dept Oral & Maxillofacial Surg, Div Oral & Maxillofacial Reconstruct Surg, Kitakyushu, Fukuoka, Japan

[2] Kyushu Dent Coll, Div Infect & Mol Biol, Dept Hlth Promot, Kitakyushu, Fukuoka 803, Japan

[3] Kagawa Prefectural Cent Hosp, Div Oral & Maxillofacial Surg, Takamatsu, Kagawa, Japan

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2008年 / 216卷 / 03期

关键词：

D O I：

10.1002/jcp.21468

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 Smad 1/5/8 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.

引用

页码：844 / 850

页数：7

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