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Staphylococcus aureus peptidoglycan promotes osteoclastogenesis via TLR2-mediated activation of the NF-κB/NFATc1 signaling pathway.

Abstract：

:Staphylococcus aureus (S. aureus) peptidoglycan (PGN-sa), the major cell wall component of S. aureus, has been demonstrated to be an important virulence factor in the pathogenesis of S. aureus-induced osteomyelitis. However, the exact role of PGN-sa in osteoclastogenesis during S. aureus-induced osteomyelitis and its underlying molecular mechanisms remain unclear. In this study, we found that PGN-sa promoted receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation. Quantitative real-time polymerase chain reaction results showed that the mRNA expression of osteoclast-specific marker genes, including tartrate-resistant acid phosphatase, cathepsin K, matrix metalloproteinase-9, and calcitonin receptor was upregulated by PGN-sa treatment. The results of enzyme linked immunosorbent assay showed that PGN-sa promoted the production of proinflammatory cytokines in mouse bone marrow macrophages (mBMMs) treated with RANKL. PGN-sa enhanced RANKL-stimulated protein expression of Toll-like receptor 2 (TLR2), p-IκBα, and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). Luciferase reporter assay showed that PGN-sa increased the transcriptional activity of TLR2 and NF-κB in mBMMs treated with RANKL. In addition, we found that downregulation of TLR2 attenuated the effect of PGA-sa on RANKL-induced osteoclastogenesis and activation of the NF-κB/NFATc1 signaling pathway. Taken together, this study revealed that PGN-sa promotes osteoclast formation via TLR2-mediated activation of the NF-κB/NFATc1 signaling pathway, revealing a potential effect of PGN-sa on osteomyelitis. These findings provide new insights into the pathogenic role of PGN-sa in S. aureus-induced osteomyelitis and may help to develop new therapeutic strategies for osteomyelitis.

journal_name

Am J Transl Res

journal_title

American journal of translational research

authors

Cao F,Zhou W,Liu G,Xia T,Liu M,Mi B,Liu Y

subject

Has Abstract

pub_date

2017-11-15 00:00:00

pages

5022-5030

issue

issn

1943-8141

journal_volume

pub_type

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Staphylococcus aureus peptidoglycan promotes osteoclastogenesis via TLR2-mediated activation of the NF-κB/NFATc1 signaling pathway.