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

Abstract

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.

Icariin Promotes Tendon-Bone Healing during Repair of Rotator Cuff Tears: A Biomechanical and Histological Study

“…ICA was originally proven to be protective against metabolic bone disease, especially osteoporosis [19,20,21]. Previous in vivo studies have shown that ICA could prevent ovariectomy-induced bone loss and restore femoral strength [20,21].…”

Equol promotes rat osteoblast proliferation and differentiation through activating estrogen receptor

“…Inhibition of PKCα activity in osteoblasts results in a marked decrease in mitogenactivated protein kinase activity, which is known to play an important role in the proliferation of cells, leading to a significant decrease in proliferation (Lampasso et al, 2002); on the other hand, activation of PKCα promotes human osteoblast proliferation (Villa et al, 2003;Hsieh et al, 2010;Liang et al, 2012). In rat and human osteoblast-like cell lines, PKC signaling can induce the transcription of osteocalcin (Boguslawski et al, 2000).…”

The effect of hyperbaric oxygen therapy on fracture healing in nicotinized rats

“…In many studies, HBO therapy has been reported to have positive effects on bone healing. [12][13][14][15] Wu [12] and Hsieh et al, [13] in their studies investigating the effectiveness of HBO on human osteoblasts in vitro, reported that HBO increases the proliferation and differentiation of osteoblasts. Muhonen et al [15] reported in a mandibular distraction osteogenesis model they created in rabbits, that preoperative HBO application increases the cor- rupted osteoblastic activity in bones that previously received radiation, but it could not be taken to the level of the control group not receiving radiation.…”

“…[11] In studies carried out recently, it has been stated that HBO treatment has positive effects on osteoblasts in addition to tissue oxygenation and increases bone healing. [12][13][14][15] We postulated that the negative effects of nicotine on fracture healing could be eliminated by the positive effects of HBO on bone metabolism. To the best of our knowledge, there are no experimental studies evaluating the effects of nicotine and HBO together in a fracture healing model using…”