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Minimum structural requirements for BMP-2-binding of heparin oligosaccharides.
- Source :
-
Biomaterials [Biomaterials] 2018 Nov; Vol. 184, pp. 41-55. Date of Electronic Publication: 2018 Aug 31. - Publication Year :
- 2018
-
Abstract
- Bone morphogenetic proteins (BMPs) are essential during tissue repair and remodeling after injury. Glycosaminoglycan (GAG) sugars are known to enhance BMP activity in vitro and in vivo; here the interactions of BMP-2 with various glycosaminoglycan classes were compared and shown to be selective for heparin over other comparable saccharides. The minimal chain lengths and specific sulfate moieties required for heparin-derived oligosaccharide binding to BMP-2, and the ability of such oligosaccharides to promote BMP-2-induced osteogenic differentiation in vitro were then determined. BMP-2 could bind to heparin hexasaccharides (dp6) and octasaccharides (dp8), but decasaccharides (dp10) were the minimum chain length required for both efficient binding of BMP-2 and consequent heparin-dependent cell responses. N-sulfation is the most important, and 6-O-sulfation moderately important for BMP-2 binding and activity, whereas 2-O-sulfation was much less critical. Bone formation assays in vivo further confirmed that dp10, N-sulfated heparin oligosaccharides were the minimal requirement for effective enhancement of BMP-2-induced bone formation. Such information is necessary for the rational design of the next generations of heparan-based devices for bone tissue repair.<br /> (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Bone Morphogenetic Protein 2 metabolism
Cell Differentiation
Cell Line
Female
Heparitin Sulfate chemistry
Mice
Osteogenesis
Protein Binding
Protein Stability
Rats, Sprague-Dawley
Recombinant Proteins chemistry
Recombinant Proteins metabolism
Surface Properties
Bone Morphogenetic Protein 2 chemistry
Heparin chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5905
- Volume :
- 184
- Database :
- MEDLINE
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 30205243
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2018.08.056