Hypoxia and reoxygenation augment bone-resorbing factor production from human periodontal ligament cells

Background: Oxygen deficiency caused by occlusal trauma and smoking may be associated with bone resorption in periodontitis. In the present study, the effects of hypoxia and reoxygenation on the production of bone-resorbing factors by cultured human periodontal ligament (PDL) cells were examined. Methods: Human PDL cells were cultured in 1 % O-2 (hypoxia), 20% O-2 (normal oxygen tension [normoxia]), or an oxygen concentration that went from 1 % to 20% (reoxygenation). The concentrations of bone-resorbing factors, i.e., vascular endothelial growth factor (VEGF), interleukin (IL)-6 and -1 beta, tumor necrosis factor-alpha (TNF-alpha), and prostaglandin E-2 (PGE(2)), in the cell culture supernatants were determined by enzyme-linked immunosorbent assay. Expression of the corresponding mRNAs was detected by reverse transcription-polymerase chain reaction. Results: Significantly higher extracellular concentrations of VEGF and IL-6 were detected along with greater corresponding mRNA expression in the hypoxia group compared to the normoxia group. The protein production and mRNA expression of IL-1 beta were observed only in the hypoxia group. Neither TNF-alpha nor PGE(2) was detectable in samples from either group, whereas cyclooxygenase-2 mRNA was detected. However, PGE(2) was detected after reoxygenation. Furthermore, VEGF and IL-6 and -1 beta production also tended to increase in extracellular concentration and mRNA level after reoxygenation. Conclusion: Hypoxia and reoxygenation may stimulate the PDL to produce VEGF, IL-6 and -1 beta, and PGE(2), which could result in the resorption of alveolar bone in periodontitis.