Kanzaki Shin, Takahashi Tetsu, Kanno Takahiro, Ariyoshi Wataru, Shinmyouzu Kouhei, Tujisawa Toshiyuki, Nishihara Tatsuji
Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu, Japan.
J Cell Physiol. 2008 Sep;216(3):844-50. doi: 10.1002/jcp.21468.
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.
肝素通过与多种细胞外分子结合表现出多种生物学活性，并在骨代谢中发挥关键作用。然而，肝素在骨形态发生蛋白（BMP）生物学活性中的作用仍不清楚。在本研究中，我们检测了肝素是否对体外BMP-2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精确机制。我们的结果表明，肝素抑制了用BMP-2培养的成骨细胞中的碱性磷酸酶（ALP）活性和矿化。发现肝素可抑制osterix、Runx2、ALP和骨钙素的mRNA表达，以及Smad1/5/8和p38 MAPK的磷酸化。此外，肝素与BMP-2和BMP受体（BMPR）均结合。这些结果表明，肝素抑制BMP-2与BMPR的结合，并在体外抑制BMP-2的成骨活性。
