Minimum structural requirements for BMP-2-binding of heparin oligosaccharides
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...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2020
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| Online Access: | https://hdl.handle.net/10356/143973 |
| _version_ | 1811695598140653568 |
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| author | Smith, Raymond A. A. Murali, Sadasivam Rai, Bina Lu, Xiaohua Lim, Zophia Xue Hui Lee, Jaslyn J. L. Nurcombe, Victor Cool, Simon M. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Smith, Raymond A. A. Murali, Sadasivam Rai, Bina Lu, Xiaohua Lim, Zophia Xue Hui Lee, Jaslyn J. L. Nurcombe, Victor Cool, Simon M. |
| author_sort | Smith, Raymond A. A. |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T07:26:01Z |
| format | Journal Article |
| id | ntu-10356/143973 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:26:01Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1439732020-10-06T01:26:38Z Minimum structural requirements for BMP-2-binding of heparin oligosaccharides Smith, Raymond A. A. Murali, Sadasivam Rai, Bina Lu, Xiaohua Lim, Zophia Xue Hui Lee, Jaslyn J. L. Nurcombe, Victor Cool, Simon M. Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Heparin Glycosaminoglycan 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. 2020-10-06T01:26:38Z 2020-10-06T01:26:38Z 2018 Journal Article 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 1878-5905 https://hdl.handle.net/10356/143973 10.1016/j.biomaterials.2018.08.056 30205243 184 41 55 en Biomaterials © 2018 Elsevier Ltd. All rights reserved. |
| spellingShingle | Science::Medicine Heparin Glycosaminoglycan Smith, Raymond A. A. Murali, Sadasivam Rai, Bina Lu, Xiaohua Lim, Zophia Xue Hui Lee, Jaslyn J. L. Nurcombe, Victor Cool, Simon M. Minimum structural requirements for BMP-2-binding of heparin oligosaccharides |
| title | Minimum structural requirements for BMP-2-binding of heparin oligosaccharides |
| title_full | Minimum structural requirements for BMP-2-binding of heparin oligosaccharides |
| title_fullStr | Minimum structural requirements for BMP-2-binding of heparin oligosaccharides |
| title_full_unstemmed | Minimum structural requirements for BMP-2-binding of heparin oligosaccharides |
| title_short | Minimum structural requirements for BMP-2-binding of heparin oligosaccharides |
| title_sort | minimum structural requirements for bmp 2 binding of heparin oligosaccharides |
| topic | Science::Medicine Heparin Glycosaminoglycan |
| url | https://hdl.handle.net/10356/143973 |
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