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

• Published in: Connective tissue research 2010-12, Vol.51 (6), p.497-509
• Main Authors: Hsieh, Cheng-Pu, Chiou, Ya-Ling, Lin, Ching-Yuang
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Bone Regeneration - physiology; cell cycle; Cell Cycle - physiology; Cell Line, Transformed; Cell Proliferation; FGF-2/MEK/ERK 1/2/NF-κB pathway; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - physiology; Fracture Healing - physiology; Fractures, Bone - metabolism; Fractures, Bone - pathology; Fractures, Bone - therapy; hyperbaric O; Hyperbaric Oxygenation - methods; MAP Kinase Kinase 1 - physiology; MAP Kinase Signaling System - physiology; Mice; Mitogen-Activated Protein Kinase 3 - physiology; Mitogen-Activated Protein Kinase 8 - metabolism; NF-kappa B - physiology; osteoblast; Osteoblasts - enzymology; Osteoblasts - metabolism; PKC/JNK pathway; Protein Kinase C - metabolism
• ISSN: 0300-8207; 1607-8438
• DOI: 10.3109/03008201003746679

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, p70S6K, 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 p70S6K NF-κB and PKC JNK pathways may be involved in mediating this process.