Infection by Streptococcus pyogenes induces the receptor activator of NF-kappaB ligand expression in mouse osteoblastic cells.
Group A Streptococcus pyogenes is known to induce nongonococcal septic arthritis in addition to pharyngitis, scarlet fever, and poststreptococcal sequelae. However, little is known about the interaction between S. pyogenes and bone cells. We report here that S. pyogenes strain JRS4 (M6) attached to and invaded mouse primary osteoblasts. Reverse transcription-PCR demonstrated that S. pyogenes infection of osteoblasts stimulated expression of mRNA for the receptor activator of NF-kappaB ligand (RANKL). Western blot analysis followed by ligand precipitation with the receptor activator of NF-kappaB receptor showed that there was an increase in RANKL protein in infected osteoblasts. Production of interleukin-6 was also stimulated, but no production of interleukin-1beta or tumor necrosis factor alpha was observed. Stimulation of RANKL production was not observed in osteoblasts stimulated with heat-inactivated S. pyogenes, suggesting that an active interaction of S. pyogenes with osteoblasts is essential for this phenomenon. A Western blot analysis performed with antibodies specific for phosphorylated signal transduction proteins demonstrated that S. pyogenes infection induces phosphorylation of p38 mitogen-activated protein kinase. A specific inhibitor of this kinase, SB203580, inhibited RANKL production by infected osteoblasts. These results suggest that infection of osteoblasts by S. pyogenes stimulates RANKL production and may trigger bone destruction in infected bone tissue.
Okahashi
Nobuo
N
Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Japan. okahashi@dent.osaka-u.ac.jp
Sakurai
Atsuo
A
Nakagawa
Ichiro
I
Fujiwara
Taku
T
Kawabata
Shigetada
S
Amano
Atsuo
A
Hamada
Shigeyuki
S
D000818:Animals; D001422:Bacterial Adhesion; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010006:Osteoblasts / Q000382:microbiology*; D053245:RANK Ligand; D012333:RNA, Messenger / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013297:Streptococcus pyogenes / Q000472:pathogenicity* / Q000502:physiology; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
D002352:Carrier Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases