Heparin inhibits BMP-2 osteogenic bioactivity by binding to both BMP-2 and BMP receptor
Heparin inhibits BMP-2 osteogenic bioactivity by binding to both BMP-2 and BMP receptor
复制标题
DOI：
10.1002/jcp.21468
复制
发表时间：
2008-09-01
影响因子：
5.6
通讯作者：
Nishihara, Tatsuji
中科院分区：
文献类型：
--
作者：
Kanzaki, Shin;Takahashi, Tetsu;Nishihara, Tatsuji
肝素通过与多种细胞外分子结合而发挥多种生物学活性，在骨代谢中起关键作用。然而，肝素在骨形态发生蛋白（BMP）生物活性中的作用仍不清楚。在本研究中，我们研究了肝素是否对BMP-2体外诱导的成骨细胞分化有影响，并阐明了肝素调节该分子诱导的骨代谢的确切机制。我们的研究结果表明，肝素抑制碱性磷酸酶（ALP）的活性和矿化成骨细胞与BMP-2培养。肝素可抑制Osterix、Runx 2、ALP和骨钙素的mRNA表达，并抑制Smad 1/5/8和p38 MAPK的磷酸化。此外，肝素结合BMP-2和BMP受体（BMPR）。这些结果表明，肝素抑制BMP-2-BMPR结合，并抑制BMP-2体外成骨活性。
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.