The cellular and molecular mechanism through which hyperbaric oxygen therapy (HBO) improves osteonecrosis (ON) is unclear. The present study therefore examined the effect of HBO, pressure and hyperoxia on RANKL‐induced osteoclast formation in RAW 264.7 cells and human peripheral blood monocytes (PBMC). Daily exposure to HBO (2.4 ATA, 97% O2, 90 min), hyperbaric pressure (2.4 ATA, 8.8% O2, 90 min) or normobaric hyperoxia (1 ATA, 95% O2, 90 min) significantly decreased RANKL‐induced osteoclast formation and bone resorption in normoxic conditions. HBO had a more pronounced anti‐osteoclastic effect than hyperoxia or pressure alone and also directly inhibited osteoclast formation and resorption in hypoxic conditions a hallmark of many osteolytic skeletal disorders. The suppressive action of HBO was at least in part mediated through a reduction in RANK, NFATc1, and Dc‐STAMP expression and inhibition of hypoxia‐induced HIF‐1α mRNA and protein expression. This data provides mechanistic evidence supporting the use of HBO as an adjunctive therapy to prevent osteoclast formation and bone loss associated with low oxygen partial pressure.
The data from this study shows that HBO has a direct suppressive effect on osteoclast differentiation and activity in normoxic and hypoxic conditions. This would appear to be associated with a reduced response to RANKL secondary to changes in HIF, RANK, and NFATc1 expression. Thus the beneficial effect of adjunctive HBO on necrotic bone may occur in part due to a reduction in aberrant osteoclast activity. This provides evidence supporting the use of HBO as an adjunctive therapy to prevent osteoclast formation in a range of skeletal disorders associated with hypoxia.
Hadil Al Hadi, Gary R. Smerdon,Simon W. Fox, 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1839–1844, 2013
