BACKGROUND: The source and mechanisms leading to osteoclast (OC) generation during tooth movement are not clearly understood. We hypothesized that during tooth movement, OC differentiate from peripheral blood mononuclear cells (PBMNC) downstream of the global hypoxia-inducible transcription factor hypoxia-inducible factor (HIF)-1α. OBJECTIVE: The objective of this study was to demonstrate up-regulation of OC growth factors from osteoblasts (OB) and subsequent conversion of PBMNC into functional OC under hypoxic stress. MATERIAL AND METHODS: Human primary PBMNC were cocultured with/without OB and subjected to either hypoxia (2.5% O2) or normoxia (21% O2) over 14 days. Levels of HIF, vascular endothelial growth factor (VEGF) and receptor activator for nuclear factor kappa-β ligand (RANKL) were measured. Conversion of PBMNC into OC was measured using resorption and TRAP assays. RESULTS: Functional OC were only observed in response to hypoxia during coculture of PBMNC and OB and only after up-regulation of HIF, VEGF and RANKL in the hypoxic conditions. YC-1, a HIF inhibitor, reduced OC formation in response to hypoxia. CONCLUSION: Hypoxia triggers the differentiation of PBMNC into functional OC in the presence of OB in a HIF-dependent manner as would occur during orthodontic loading of the periodontal ligament space.
BACKGROUND: The source and mechanisms leading to osteoclast (OC) generation during tooth movement are not clearly understood. We hypothesized that during tooth movement, OC differentiate from peripheral blood mononuclear cells (PBMNC) downstream of the global hypoxia-inducible transcription factor hypoxia-inducible factor (HIF)-1α. OBJECTIVE: The objective of this study was to demonstrate up-regulation of OC growth factors from osteoblasts (OB) and subsequent conversion of PBMNC into functional OC under hypoxic stress. MATERIAL AND METHODS:Human primary PBMNC were cocultured with/without OB and subjected to either hypoxia (2.5% O2) or normoxia (21% O2) over 14 days. Levels of HIF, vascular endothelial growth factor (VEGF) and receptor activator for nuclear factor kappa-β ligand (RANKL) were measured. Conversion of PBMNC into OC was measured using resorption and TRAP assays. RESULTS: Functional OC were only observed in response to hypoxia during coculture of PBMNC and OB and only after up-regulation of HIF, VEGF and RANKL in the hypoxic conditions. YC-1, a HIF inhibitor, reduced OC formation in response to hypoxia. CONCLUSION:Hypoxia triggers the differentiation of PBMNC into functional OC in the presence of OB in a HIF-dependent manner as would occur during orthodontic loading of the periodontal ligament space.
Authors: Anja Bastian; Jessica E Thorpe; Bryan C Disch; Lora C Bailey-Downs; Aleem Gangjee; Ravi K V Devambatla; Jim Henthorn; Kenneth M Humphries; Shraddha S Vadvalkar; Michael A Ihnat Journal: J Pharmacol Exp Ther Date: 2015-02-26 Impact factor: 4.030
Authors: Jeffrey L Ebersole; Michael John Novak; Luis Orraca; Janis Martinez-Gonzalez; Sreenatha Kirakodu; Kuey C Chen; Arnold Stromberg; Octavio A Gonzalez Journal: Immunology Date: 2018-02-14 Impact factor: 7.397
Authors: Jaikitry Rawal; Mark J W McPhail; Gamumu Ratnayake; Pearl Chan; John Moxham; Stephen D R Harridge; Nicholas Hart; Hugh E Montgomery; Zudin A Puthucheary Journal: Crit Care Date: 2015-04-14 Impact factor: 9.097