1. Minimum structural requirements for BMP-2-binding of heparin oligosaccharides.
- Author
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Smith, Raymond A.A., Murali, Sadasivam, Rai, Bina, Lu, Xiaohua, Lim, Zophia Xue Hui, Lee, Jaslyn J.L., Nurcombe, Victor, and Cool, Simon M.
- Subjects
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OLIGOSACCHARIDES , *HEPARIN , *GLUCOSIDES , *GLYCANS , *MONOSACCHARIDES - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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