Hyperbaric oxygen-stimulated proliferation and growth of osteoblasts may be mediated through the FGF-2/MEK/ERK 1/2/NF-κB and PKC/JNK pathways.
We investigated whether the hyperbaric oxygen (O₂) could promote the proliferation of growth-arrested osteoblasts in vitro and the mechanisms involved in this process. Osteoblasts were exposed to different combinations of saturation and pressure of O₂ and evaluated at 3 and 7 days. Control cells were cultured under ambient O₂ and normal pressure [1 atmosphere (ATA)]; high-pressure group cells were treated with high pressure (2.5 ATA) twice daily; high-O₂ group cells were treated with a high concentration O₂ (50% O₂) twice daily; and high pressure plus high-O₂ group cells were treated with high pressure (2.5 ATA) and a high concentration O₂ (50% O₂) twice daily. Hyperbaric O₂ significantly promoted osteoblast proliferation and cell cycle progression after 3 days of treatment. Hyperbaric O₂ treatment stimulated significantly increased mRNA expression of fibroblast growth factor (FGF)-2 as well as protein expression levels of Akt, p70(S6K), phosphorylated ERK, nuclear factor (NF)-κB, protein kinase C (PKC)α, and phosphorylated c-Jun N-terminal kinase (JNK). Our findings indicate that high pressure and high O₂ saturation stimulates growth-arrested osteoblasts to proliferate. These findings suggest that the proliferative effects of hyperbaric O₂ on osteoblasts may contribute to the recruitment of osteoblasts at the fracture site. The FGF-2/MEK/ERK 1/2/Akt/p70(S6K)/NF-κB and PKC/JNK pathways may be involved in mediating this process.
Hsieh
Cheng-Pu
CP
Orthopaedic Surgery Department and Hyperbaric Center, Changhua Christian Hospital, Changhua, Taiwan, ROC.
Chiou
Ya-Ling
YL
Lin
Ching-Yuang
CY
D016475:3T3 Cells; D000818:Animals; D001861:Bone Regeneration / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000502:physiology; D017102:Fracture Healing / Q000502:physiology; D050723:Fractures, Bone / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006931:Hyperbaric Oxygenation / Q000379:methods*; D048369:MAP Kinase Kinase 1 / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology*; D010006:Osteoblasts / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism
D016328:NF-kappa B; D016222:Fibroblast Growth Factor 2; D011493:Protein Kinase C; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse