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|Title:||Minimum structural requirements for BMP-2-binding of heparin oligosaccharides||Authors:||Smith, Raymond A. A.
Lim, Zophia Xue Hui
Lee, Jaslyn J. L.
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.||URI:||https://hdl.handle.net/10356/143973||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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