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

Shin Kanzaki, Tetsu Takahashi, Takahiro Kanno, Wataru Ariyoshi, Kouhei Shinmyouzu, Toshiyuki Tujisawa, Tatsuji Nishihara

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

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 osteoblasts 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.

Original languageEnglish
Pages (from-to)844-850
Number of pages7
JournalJournal of Cellular Physiology
Volume216
Issue number3
DOIs
Publication statusPublished - 2008 Sep 1
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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