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Hypoxia signalling manipulation for bone regeneration

Published online by Cambridge University Press:  22 April 2015

Justin Drager ,
Edward J. Harvey  and
Jake Barralet
Justin Drager
Affiliation:
Division of Orthopaedic Surgery, McGill University Health Centre, Montreal, Quebec, Canada
Edward J. Harvey
Affiliation:
Division of Orthopaedic Surgery, McGill University Health Centre, Montreal, Quebec, Canada
Jake Barralet*
Affiliation:
Division of Orthopaedic Surgery, McGill University Health Centre, Montreal, Quebec, Canada
*
*Corresponding author: Division of Orthopaedic Surgery, Montreal General Hospital L9-125, 1650 Cedar Avenue, Montreal Quebec, CanadaH3G 1A4. E-mail: Jake.barralet@mcgill.ca
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Abstract

Hypoxia-inducible factor (HIF) signalling is intricately involved in coupling angiogenesis and osteogenesis during bone development and repair. Activation of HIFs in response to a hypoxic bone micro-environment stimulates the transcription of multiple genes with effects on angiogenesis, precursor cell recruitment and differentiation. Substantial progress has been made in our understanding of the molecular mechanisms by which oxygen content regulates the levels and activity of HIFs. In particular, the discovery of the role of oxygen-dependent hydroxylase enzymes in modulating the activity of HIF-1α has sparked interest in potentially promising therapeutic strategies in multiple clinical fields and most recently bone healing. Several small molecules, termed hypoxia mimics, have been identified as activators of the HIF pathway and have demonstrated augmentation of both bone vascularity and bone regeneration in vivo. In this review we discuss key elements of the hypoxic signalling pathway and its role in bone regeneration. Current strategies for the manipulation of this pathway for enhancing bone repair are presented with an emphasis on recent pre-clinical in vivo investigations. These findings suggest promising approaches for the development of therapies to improve bone repair and tissue engineering strategies.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 17 , 2015 , e6
Copyright
Copyright © Cambridge University Press 2015 

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