Effect of heparin on osteoinductive activity of bone morphogenetic protein 6 (BMP6)

Brkljačić, Jelena (2013) Effect of heparin on osteoinductive activity of bone morphogenetic protein 6 (BMP6). Doctoral thesis, Faculty of Science > Department of Biology.

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Abstract

Secondary osteoporosis is a complication of long-term heparin therapy. We investigated the role of heparin in BMP6 signaling and osteogenic activity in vitro in C2C12-BRE-Luc mouse myoblast cell line and in vivo in two osteoporosis models in mice. BMP6 specifically binds to heparin, which inhibits BMP6-induced phosphorylation of Smad1/5/8 in C2C12-BRE-Luc cells. Pretreatment with chlorate and heparinase III inhibits BMP6 signaling, for which the N-and O-sulfate structures are necessary. Heparin inhibits BMP6-induced expression of alkaline phosphatase and osteocalcin. In the subcutaneous test heparin dose-dependently inhibits BMP6-induced formation of new bone and cartilage. In the model of postmenopausal osteoporosis heparin dose-dependently inhibits the ability of BMP6 to improve the quality of the bone, as shown by DEXA and μCT. In the model of heparin-induced osteoporosis simultaneous treatment with BMP6 prevents the negative effect of heparin on bone, as shown by the lack of significant differences in BMD and trabecular bone parameters compared to control animals. These results show for the first time that binding of heparin to BMP6 may contribute to the development of heparin-induced osteoporosis and that heparin therapy in combination with BMP6 can prevent heparin-induced osteoporosis.

Item Type: Thesis (Doctoral thesis)
Keywords: heparin, bone morphogenetic protein 6, osteoporosis
Supervisor: Vukičević, Slobodan
Date: 2013
Number of Pages: 116
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Grozdana Sirotic
Date Deposited: 11 Feb 2014 12:11
Last Modified: 22 Sep 2014 09:56
URI: http://digre.pmf.unizg.hr/id/eprint/412

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