Bone marrow-derived heparan sulfate potentiates the osteogenic activity of bone morphogenetic protein-2 (BMP-2)

Autor: Ling Ling, Sadasivam Murali, Gary S. Stein, Bina Rai, Andre J. van Wijnen, Diah S. Bramono, Wei Theng Poh, Zophia X.H. Lim, Victor Nurcombe, Simon M. Cool
Rok vydání: 2012
Předmět:
animal structures
Histology
Physiology
Endocrinology
Diabetes and Metabolism
Sus scrofa
Biological Availability
Bone Morphogenetic Protein 2
Bone Marrow Cells
Bone healing
Choristoma
Disaccharides
Bone morphogenetic protein 2
Article
Cell Line
Rats
Sprague-Dawley
Mice
chemistry.chemical_compound
Osteogenesis
medicine
Animals
Humans
Bone morphogenetic protein receptor
Bone Morphogenetic Protein Receptors
Type I
Chromatography
High Pressure Liquid
Heparin
Protein Stability
Chemistry
Cell Differentiation
Drug Synergism
Heparan sulfate
Chromatography
Ion Exchange
Rats
Cell biology
Bone morphogenetic protein 7
medicine.anatomical_structure
Bone growth factor
Biochemistry
Culture Media
Conditioned
embryonic structures
Cattle
Female
Heparitin Sulfate
Bone marrow
Stromal Cells
Carrier Proteins
Protein Binding
medicine.drug
Zdroj: Bone. 50:954-964
ISSN: 8756-3282
DOI: 10.1016/j.bone.2011.12.013
Popis: Lowering the efficacious dose of bone morphogenetic protein-2 (BMP-2) for the repair of critical-sized bone defects is highly desirable, as supra-physiological amounts of BMP-2 have an increased risk of side effects and a greater economic burden for the healthcare system. To address this need, we explored the use of heparan sulfate (HS), a structural analog of heparin, to enhance BMP-2 activity. We demonstrate that HS isolated from a bone marrow stromal cell line (HS-5) and heparin each enhances BMP-2-induced osteogenesis in C2C12 myoblasts through increased ALP activity and osteocalcin mRNA expression. Commercially available HS variants from porcine kidney and bovine lung do not generate effects as great as HS5. Heparin and HS5 influence BMP-2 activity by (i) prolonging BMP-2 half-life, (ii) reducing interactions between BMP-2 with its antagonist noggin, and (iii) modulating BMP2 distribution on the cell surface. Importantly, long-term supplementation of HS5 but not heparin greatly enhances BMP-2-induced bone formation in vitro and in vivo. These results show that bone marrow-derived HS effectively supports bone formation, and suggest its applicability in bone repair by selectively facilitating the delivery and bioavailability of BMP-2.
Databáze: OpenAIRE
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