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

摘要: Lowering the efficacious dose of bone morphogenetic protein-2 (BMP-2) for repair critical-sized defects is highly desirable, as supra-physiological amounts BMP-2 have an increased risk side effects and a greater economic burden healthcare system. To address this need, we explored use heparan sulfate (HS), structural analog heparin, to enhance activity. We demonstrate that HS isolated from marrow stromal cell line (HS-5) heparin each enhances BMP-2-induced osteogenesis in C2C12 myoblasts through ALP activity osteocalcin mRNA expression. Commercially available variants porcine kidney bovine lung do not generate great HS5. Heparin HS5 influence by (i) prolonging half-life, (ii) reducing interactions between with its antagonist noggin, (iii) modulating BMP2 distribution on surface. Importantly, long-term supplementation but greatly formation vitro vivo. These results show marrow-derived effectively supports formation, suggest applicability selectively facilitating delivery bioavailability BMP-2.