Hypoxia mimetics restore bone biomineralisation in hyperglycaemic environments.

Autor: Rezaei A; Division of Surgery & Interventional Science, University College London, 9th Floor Royal Free Hospital, London, NW3 2QG, UK., Li Y; Division of Surgery & Interventional Science, University College London, 9th Floor Royal Free Hospital, London, NW3 2QG, UK., Turmaine M; Department of Cell & Developmental Biology, University College London, London, WC1E 6BT, UK., Bertazzo S; Department of Medical Physics & Biomedical Engineering, University College London, London, WC1E 6BT, UK., Howard CA; Department of Physics & Astronomy, University College London, London, WC1E 6BT, UK., Arnett TR; Department of Cell & Developmental Biology, University College London, London, WC1E 6BT, UK., Shakib K; Division of Surgery & Interventional Science, University College London, 9th Floor Royal Free Hospital, London, NW3 2QG, UK. k.shakib@ucl.ac.uk., Jell G; Division of Surgery & Interventional Science, University College London, 9th Floor Royal Free Hospital, London, NW3 2QG, UK. g.jell@ucl.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Aug 17; Vol. 12 (1), pp. 13944. Date of Electronic Publication: 2022 Aug 17.
DOI: 10.1038/s41598-022-18067-1
Abstrakt: Diabetic patients have an increased risk of fracture and an increased occurrence of impaired fracture healing. Diabetic and hyperglycaemic conditions have been shown to impair the cellular response to hypoxia, via an inhibited hypoxia inducible factor (HIF)-1α pathway. We investigated, using an in vitro hyperglycaemia bone tissue engineering model (and a multidisciplinary bone characterisation approach), the differing effects of glucose levels, hypoxia and chemicals known to stabilise HIF-1α (CoCl 2 and DMOG) on bone formation. Hypoxia (1% O 2 ) inhibited bone nodule formation and resulted in discrete biomineralisation as opposed to the mineralised extracellular collagen fibres found in normoxia (20% O 2 ). Unlike hypoxia, the use of hypoxia mimetics did not prevent nodule formation in normal glucose level. Hyperglycaemic conditions (25 mM and 50 mM glucose) inhibited biomineralisation. Interestingly, both hypoxia mimetics (CoCl 2 and DMOG) partly restored hyperglycaemia inhibited bone nodule formation. These results highlight the difference in osteoblast responses between hypoxia mimetics and actual hypoxia and suggests a role of HIF-1α stabilisation in bone biomineralisation that extends that of promoting neovascularisation, or other system effects associated with hypoxia and bone regeneration in vivo. This study demonstrates that targeting the HIF pathway may represent a promising strategy for bone regeneration in diabetic patients.
(© 2022. The Author(s).)
Databáze: MEDLINE
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