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Title: Minimum structural requirements for BMP-2-binding of heparin oligosaccharides
Authors: Smith, Raymond A. A.
Murali, Sadasivam
Rai, Bina
Lu, Xiaohua
Lim, Zophia Xue Hui
Lee, Jaslyn J. L.
Nurcombe, Victor
Cool, Simon M.
Keywords: Science::Medicine
Issue Date: 2018
Source: Smith, R. A. A., Murali, S., Rai, B., Lu, X., Lim, Z. X. H., Lee, J. J. L., ... Cool, S. M. (2018). Minimum structural requirements for BMP-2-binding of heparin oligosaccharides. Biomaterials, 184, 41-55. doi:10.1016/j.biomaterials.2018.08.056
Journal: Biomaterials
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.
ISSN: 1878-5905
DOI: 10.1016/j.biomaterials.2018.08.056
Rights: © 2018 Elsevier Ltd. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:LKCMedicine Journal Articles

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