Heparin inhibits BMP-2 osteogenic bioactivity by binding to both BMP-2 and BMP receptor.
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.
Kanzaki
Shin
S
Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu, Japan.
Takahashi
Tetsu
T
Kanno
Takahiro
T
Ariyoshi
Wataru
W
Shinmyouzu
Kouhei
K
Tujisawa
Toshiyuki
T
Nishihara
Tatsuji
T
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2; D052004:Bone Morphogenetic Protein Receptors / Q000235:genetics / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002113:Calcification, Physiologic; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D006493:Heparin / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013552:Swine; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D000925:Anticoagulants; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D006493:Heparin; D052004:Bone Morphogenetic Protein Receptors; D000469:Alkaline Phosphatase