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- Publisher Website: 10.1042/BJ20101096
- Scopus: eid_2-s2.0-79952159933
- PMID: 21204783
- WOS: WOS:000288613900013
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Article: Identification of a DNA aptamer that inhibits sclerostin's antagonistic effect on Wnt signalling
Title | Identification of a DNA aptamer that inhibits sclerostin's antagonistic effect on Wnt signalling | ||||||
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Authors | |||||||
Keywords | G-quadruplex Isothermal titration calorimetry (ITC) Sclerosteosis Sclerostin Systematic evolution of ligands by exponential enrichment (SELEX) Wnt signalling | ||||||
Issue Date | 2011 | ||||||
Publisher | Portland Press Ltd. The Journal's web site is located at http://www.biochemj.org | ||||||
Citation | Biochemical Journal, 2011, v. 434 n. 3, p. 493-501 How to Cite? | ||||||
Abstract | Sclerostin is an extracellular negative regulator of bone formation that is a recognized therapeutic target for osteoporosis therapy. In the present study, we performed DNA aptamer selection against sclerostin, then characterized aptamer-sclerostin binding and the ability to inhibit sclerostin function in cell culture. We show that a selected DNA aptamer was highly selective for binding to sclerostin with affinities in the nanomolar range as determined by solid-phase assays and by isothermal titration calorimetry. Binding between sclerostin and the aptamer was exothermic and enthalpically driven. CD confirmed that the aptamer had temperature-dependent parallel G-quadruplex characteristics. The aptamer was stabilized with 3′ inverted thymidine to investigate efficacy at inhibiting sclerostin function in cell culture. The stabilized DNA aptamer showed potent and specific dose-dependent inhibition of sclerostin's antagonistic effect on Wnt activity using a reporter assay. Taken together, the present findings suggest an alternative approach to inhibiting sclerostin function with therapeutic potential. © The Authors Journal compilation © 2011 Biochemical Society. | ||||||
Persistent Identifier | http://hdl.handle.net/10722/133578 | ||||||
ISSN | 2023 Impact Factor: 4.4 2023 SCImago Journal Rankings: 1.612 | ||||||
ISI Accession Number ID |
Funding Information: This work was supported by the Hong Kong Research Grants Council under the General Research Fund scheme [grant number HKU 7488/06M] and an Area of Excellence Grant [grant number AoE/M-04/04]. | ||||||
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Grants |
DC Field | Value | Language |
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dc.contributor.author | Shum, KT | en_HK |
dc.contributor.author | Chan, C | en_HK |
dc.contributor.author | Leung, CM | en_HK |
dc.contributor.author | Tanner, JA | en_HK |
dc.date.accessioned | 2011-05-24T02:11:12Z | - |
dc.date.available | 2011-05-24T02:11:12Z | - |
dc.date.issued | 2011 | en_HK |
dc.identifier.citation | Biochemical Journal, 2011, v. 434 n. 3, p. 493-501 | en_HK |
dc.identifier.issn | 0264-6021 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/133578 | - |
dc.description.abstract | Sclerostin is an extracellular negative regulator of bone formation that is a recognized therapeutic target for osteoporosis therapy. In the present study, we performed DNA aptamer selection against sclerostin, then characterized aptamer-sclerostin binding and the ability to inhibit sclerostin function in cell culture. We show that a selected DNA aptamer was highly selective for binding to sclerostin with affinities in the nanomolar range as determined by solid-phase assays and by isothermal titration calorimetry. Binding between sclerostin and the aptamer was exothermic and enthalpically driven. CD confirmed that the aptamer had temperature-dependent parallel G-quadruplex characteristics. The aptamer was stabilized with 3′ inverted thymidine to investigate efficacy at inhibiting sclerostin function in cell culture. The stabilized DNA aptamer showed potent and specific dose-dependent inhibition of sclerostin's antagonistic effect on Wnt activity using a reporter assay. Taken together, the present findings suggest an alternative approach to inhibiting sclerostin function with therapeutic potential. © The Authors Journal compilation © 2011 Biochemical Society. | en_HK |
dc.language | eng | en_US |
dc.publisher | Portland Press Ltd. The Journal's web site is located at http://www.biochemj.org | en_HK |
dc.relation.ispartof | Biochemical Journal | en_HK |
dc.rights | The final version of record is available at http://www.biochemj.org/bj/434/0493/bj4340493.htm | - |
dc.subject | G-quadruplex | en_HK |
dc.subject | Isothermal titration calorimetry (ITC) | en_HK |
dc.subject | Sclerosteosis | en_HK |
dc.subject | Sclerostin | en_HK |
dc.subject | Systematic evolution of ligands by exponential enrichment (SELEX) | en_HK |
dc.subject | Wnt signalling | en_HK |
dc.subject.mesh | Aptamers, Nucleotide - chemistry - pharmacology | - |
dc.subject.mesh | Bone Morphogenetic Proteins - antagonists and inhibitors - chemistry | - |
dc.subject.mesh | Calorimetry | - |
dc.subject.mesh | Thermodynamics | - |
dc.subject.mesh | Wnt Proteins - physiology | - |
dc.title | Identification of a DNA aptamer that inhibits sclerostin's antagonistic effect on Wnt signalling | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0264-6021&volume=434&issue=3&spage=493&epage=501&date=2011&atitle=Identification+of+a+DNA+aptamer+that+inhibits+sclerostin%27s+antagonistic+effect+on+Wnt+signaling | - |
dc.identifier.email | Tanner, JA:jatanner@hku.hk | en_HK |
dc.identifier.authority | Tanner, JA=rp00495 | en_HK |
dc.description.nature | postprint | - |
dc.identifier.doi | 10.1042/BJ20101096 | en_HK |
dc.identifier.pmid | 21204783 | - |
dc.identifier.scopus | eid_2-s2.0-79952159933 | en_HK |
dc.identifier.hkuros | 185114 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-79952159933&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 434 | en_HK |
dc.identifier.issue | 3 | en_HK |
dc.identifier.spage | 493 | en_HK |
dc.identifier.epage | 501 | en_HK |
dc.identifier.eissn | 1470-8728 | - |
dc.identifier.isi | WOS:000288613900013 | - |
dc.publisher.place | United Kingdom | en_HK |
dc.relation.project | Developmental genomics and skeletal research | - |
dc.relation.project | Targeting sclerostin with aptamer-based inhibitors as an approach to osteoporosis therapy | - |
dc.identifier.scopusauthorid | Shum, KT=20436474600 | en_HK |
dc.identifier.scopusauthorid | Chan, C=36984609500 | en_HK |
dc.identifier.scopusauthorid | Leung, CM=41361402800 | en_HK |
dc.identifier.scopusauthorid | Tanner, JA=35513993000 | en_HK |
dc.identifier.issnl | 0264-6021 | - |