Minimum structural requirements for BMP-2-binding of heparin oligosaccharides.
In: Biomaterials, Jg. 184 (2018-11-01), S. 41-55
academicJournal
Zugriff:
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.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Titel: |
Minimum structural requirements for BMP-2-binding of heparin oligosaccharides.
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Autor/in / Beteiligte Person: | Smith, RAA ; Murali, S ; Rai, B ; Lu, X ; Lim, ZXH ; Lee, JJL ; Nurcombe, V ; Cool, SM |
Zeitschrift: | Biomaterials, Jg. 184 (2018-11-01), S. 41-55 |
Veröffentlichung: | <1995-> : Amsterdam : Elsevier Science ; <i>Original Publication</i>: [Guilford, England] : IPC Science and Technology Press, 1980-, 2018 |
Medientyp: | academicJournal |
ISSN: | 1878-5905 (electronic) |
DOI: | 10.1016/j.biomaterials.2018.08.056 |
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