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Open AccessArticle

Gadolinium Tagged Osteoprotegerin-Mimicking Peptide: A Novel Magnetic Resonance Imaging Biospecific Contrast Agent for the Inhibition of Osteoclastogenesis and Osteoclast Activity

1
Department of Surgical Research, Northwick Park Institute for Medical Research, University College London (UCL), Northwick Park & St Marks Hospitals, Watford Road, Harrow, Middlesex HA1 3UJ, UK
2
Centre for Regenerative Medicine and Devices, School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Lewes Road, Brighton BN2 4GJ, UK
3
Faculty of Science, Engineering and Computing, Penrhyn Road, Kingston University, Kingston Upon Thames KT1 2EE, UK
4
Clinical Imaging and Science Centre (CISC), Centre for Regenerative Medicine and Devices, Brighton and Sussex Medical School, Lewes Road, Brighton BN1 9RR, UK
*
Author to whom correspondence should be addressed.
Nanomaterials 2018, 8(6), 399; https://doi.org/10.3390/nano8060399
Received: 17 April 2018 / Revised: 25 May 2018 / Accepted: 28 May 2018 / Published: 2 June 2018
(This article belongs to the Special Issue Tissue Engineering and Regenerative Nanomedicine)
The control of osteoblast/osteoclast cross-talk is crucial in the bone remodelling process and provides a target mechanism in the development of drugs for bone metabolic diseases. Osteoprotegerin is a key molecule in this biosignalling pathway as it inhibits osteoclastogenesis and osteoclast activation to prevent run-away bone resorption. This work reports the synthesis of a known osteoprotegerin peptide analogue, YCEIEFCYLIR (OP3-4), and its tagging with a gadolinium chelate, a standard contrast agent for magnetic resonance imaging. The resulting contrast agent allows the simultaneous imaging and treatment of metabolic bone diseases. The gadolinium-tagged peptide was successfully synthesised, showing unaltered magnetic resonance imaging contrast agent properties, a lack of cytotoxicity, and dose-dependent inhibition of osteoclastogenesis in vitro. These findings pave the way toward the development of biospecific and bioactive contrast agents for the early diagnosis, treatment, and follow up of metabolic bone diseases such as osteoporosis and osteosarcoma. View Full-Text
Keywords: osteoclastogenesis; RANK-RANKL-OPG; mimetic peptide; Gadolinium chelate; MRI osteoclastogenesis; RANK-RANKL-OPG; mimetic peptide; Gadolinium chelate; MRI
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MDPI and ACS Style

Mbundi, L.; Meikle, S.T.; Busquets, R.; Dowell, N.G.; Cercignani, M.; Santin, M. Gadolinium Tagged Osteoprotegerin-Mimicking Peptide: A Novel Magnetic Resonance Imaging Biospecific Contrast Agent for the Inhibition of Osteoclastogenesis and Osteoclast Activity. Nanomaterials 2018, 8, 399.

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