ArticleInternational orthopaedics2013
Exogenous heparin binds and inhibits bone morphogenetic protein 6 biological activity.
Article in International orthopaedics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- Osteogenic and Angiogenic Properties of Heparin as a System for Delivery of Biomolecules for Bone Bioengineering: a Brief Critical Review.Biochemistry (Moscow) Supplement. Series B, Biomedical chemistry · 2021Article
- Review
- Copresentation of BMP-6 and RGD Ligands Enhances Cell Adhesion and BMP-Mediated Signaling.Cells · 2019Article
- Iron Supplementation Therapy, A Friend and Foe of Mycobacterial Infections?Pharmaceuticals (Basel, Switzerland) · 2019Review
- Domains with highest heparan sulfate-binding affinity reside at opposite ends in BMP2/4The Journal of biological chemistry · 2018Article
- Regulated Entry of Hepatitis C Virus into Hepatocytes.Viruses · 2017Review
- Heparin, Heparan Sulphate and the TGF-β Cytokine Superfamily.Molecules (Basel, Switzerland) · 2017Review
- Infection of Hepatocytes With HCV Increases Cell Surface Levels of Heparan Sulfate Proteoglycans, Uptake of Cholesterol and Lipoprotein, and Virus Entry by Up-regulating SMAD6 and SMAD7.Gastroenterology · 2017Article
- Article
- Correlation of bone fragments reposition and related parameters in thoracolumbar burst fractures patients.International journal of clinical and experimental medicine · 2015Article
- Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice.International orthopaedics · 2015Article
- Glycol-split nonanticoagulant heparins are inhibitors of hepcidin expression in vitro and in vivo.Blood · 2014Article
- The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing.International orthopaedics · 2014Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe purpose of this study was to explore the effect of heparin on bone morphogenetic protein 6 (BMP6) osteogenic activity.
methodsWestern blot analysis was used to confirm the binding of BMP6 to heparin and to observe its effect on BMP6 signaling in C2C12-BRE-Luc myoblasts. Real-time RT-PCR was performed for the expression analysis of alkaline phosphatase (ALP) and osteocalcin (OC) in C2C12 myoblasts treated with BMP6 and heparin for 72 hours. Rat ectopic bone formation assay was performed to explore the effect of heparin on BMP6 osteogenic activity. Two weeks following implantation the implants were analysed morphologically and histologically. A mouse osteoporotic model was used to test the ability of BMP6 to improve the bone quality in vivo in the presence of heparin, followed by DEXA and μCT analyses. Blood coagulation was tested in rats previously treated with BMP6.
resultsBMP6 specifically bound to heparin and induced Smad1/5/8 phosphorylation which was inhibited by heparin. After 48 and 72 hours of treatment, heparin inhibited BMP6-induced ALP and OC expression in C2C12 cells. Heparin dose dependently inhibited BMP6-induced new bone and cartilage formation in the rat ectopic bone formation assay, while in osteoporotic mice heparin inhibited the BMP6 potential to improve the bone quality as evidenced by decreased bone mineral density and trabecular bone parameters. Interestingly, BMP6 prevented the effect of heparin on the blood coagulation parameters.
conclusionThe interaction of BMP6 with heparin might contribute to the heparin-induced osteoporosis and blood coagulation.
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