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.
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Research Article|
February 24 2011
Identification of a DNA aptamer that inhibits sclerostin's antagonistic effect on Wnt signalling Available to Purchase
Ka To Shum;
Ka To Shum
1
1Department of Biochemistry, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China
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Celine Chan;
Celine Chan
1
1Department of Biochemistry, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China
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Ching-Man Leung;
Ching-Man Leung
1Department of Biochemistry, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China
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Julian A. Tanner
Julian A. Tanner
2
1Department of Biochemistry, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China
2To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
July 20 2010
Revision Received:
December 10 2010
Accepted:
January 04 2011
Accepted Manuscript online:
January 04 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 434 (3): 493–501.
Article history
Received:
July 20 2010
Revision Received:
December 10 2010
Accepted:
January 04 2011
Accepted Manuscript online:
January 04 2011
Citation
Ka To Shum, Celine Chan, Ching-Man Leung, Julian A. Tanner; Identification of a DNA aptamer that inhibits sclerostin's antagonistic effect on Wnt signalling. Biochem J 15 March 2011; 434 (3): 493–501. doi: https://doi.org/10.1042/BJ20101096
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