Bone marrow-derived heparan sulfate potentiates the osteogenic activity of bone morphogenetic protein-2 (BMP-2)
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Authors
Bramono, Diah S.Murali, Sadasivam
Rai, Bina
Ling, Ling
Poh, Wei Theng
Lim, Zophia Xuehui
Stein, Gary S.
Nurcombe, Victor
Van Wijnen, Andre J.
Cool, Simon M.
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2012-04-01
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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.Source
Bone. 2012 Apr;50(4):954-64. Epub 2011 Dec 28. Link to article on publisher's siteDOI
10.1016/j.bone.2011.12.013Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49585PubMed ID
22227436Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.bone.2011.12.013