Azithromycin suppresses human osteoclast formation and activity in vitro.
Azithromycin is an antibiotic with anti-inflammatory properties used as an adjunct to treat periodontitis, a common inflammatory mediated condition featuring pathologic alveolar bone resorption. This study aimed to determine the effect of azithromycin on human osteoclast formation and resorptive activity in vitro. Osteoclasts were generated from peripheral blood mononuclear cells stimulated with macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B (RANK) ligand. The effects of azithromycin at concentrations ranging from 0.5 to 40 µg/ml were tested. Osteoclast formation and activity, acidification, actin ring formation and expression of mRNA, and protein encoding for key osteoclast genes were assessed. The results demonstrated that azithromycin reduced osteoclast resorptive activity at all concentrations tested with osteoclast formation being significantly reduced at the higher concentrations (20 and 40 µg/ml). mRNA and protein expression of key osteoclast transcription factor Nuclear Factor of Activated T cells (NFATc1) was significantly reduced by azithromycin at later stages of osteoclast development (day 17). Azithromycin also reduced tumor necrosis factor receptor associated factor-6 (TRAF6) mRNA expression at day 14, and cathepsin K mRNA expression at days 14 and 17. Integrin β3 and MMP-9 mRNA expression was reduced by azithromycin at day 17 in osteoclasts cultured on dentine. The osteoclast proton pump did not appear to be affected by azithromycin, however formation of the actin ring cytoskeleton was inhibited. This study demonstrates that azithromycin inhibits human osteoclast function in vitro, which may account for at least some of the beneficial clinical effects observed with azithromycin treatment in periodontitis.
Colgate Australian Clinical Dental Research Centre, School of Dentistry, University of Adelaide, South Australia, Australia.
Siobhan C
SC
Gannon
Melissa D
MD
Cantley
David R
DR
Haynes
Robert
R
Hirsch
P Mark
PM
Bartold
D017963:Azithromycin / Q000494:pharmacology*; D058621:Blood Buffy Coat / Q000187:drug effects / Q000378:metabolism; D056657:Cathepsin K / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010518:Periodontitis / Q000188:drug therapy / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000494:pharmacology; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism
D039661:Integrin beta3; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D053246:Receptor Activator of Nuclear Factor-kappa B; D048029:TNF Receptor-Associated Factor 6; C505686:TNFRSF11A protein, human; D016173:Macrophage Colony-Stimulating Factor; D017963:Azithromycin; D056657:Cathepsin K; D020780:Matrix Metalloproteinase 9