title: Hyperbaric oxygen therapy suppresses osteoclast formation and bone resorption.
abstract: 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.
authors.affiliation: School of Biomedical and Biological Sciences, Plymouth University, Drake Circus, Plymouth, Devon, PL4 8AA, UK.
authors.forename: Hadil
authors.initials: H
authors.lastname: Al Hadi
authors.forename: Gary R
authors.initials: GR
authors.lastname: Smerdon
authors.forename: Simon W
authors.initials: SW
authors.lastname: Fox
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001862:Bone Resorption / Q000517:prevention & control*; D002478:Cells, Cultured; D006801:Humans; D006931:Hyperbaric Oxygenation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors / Q000235:genetics; D010010:Osteoclasts / Q000502:physiology*; D053245:RANK Ligand / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501589:DCSTAMP protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D053245:RANK Ligand
keywords: hyperbaric oxygen therapy; hypoxia; osteoclast; osteonecrosis