Pseudomonas aeruginosa lipopolysaccharide induces osteoclastogenesis through a toll-like receptor 4 mediated pathway in vitro and in vivo

Lei Zhuang, Jae Y. Jung, Eric W. Wang, Patrick Houlihan, Lisette Ramos, Mary Pashia, Richard A. Chole

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

OBJECTIVES: Bacterial infections near bone result in localized inflammatory osteolysis, a significant complication of chronic ear infections. While many bacterial products may be involved, lipopolysaccharide (LPS) has been implicated as a major mediator of inflammation and osteolysis. However, the mechanisms by which LPS promotes bone resorption have not been clearly established. There is no consensus on whether LPS acts directly or indirectly on osteoclast precursors (bone marrow monocytes [BMM]) to induce bone resorption. In light of the role of Pseudomonas aeruginosa, in chronic ear infections, we investigated the effects of P. aeruginosa LPS on osteoclastogenesis in vivo and in vitro. METHODS: Wild-type C57BL/6J and toll-like receptor 4 knock-out (TLR4-/-) mice received subcutaneous calvarial injections of 250 μg of P. aeruginosa LPS or phosphate buffered saline (PBS) only (n = 5 per group). Osteoclastic bone resorption was assessed histologically. The effect of P. aeruginosa LPS on bone resorption was assessed in vitro using combinations of BMMs and osteoblasts with and without functional toll-like receptor 4 (TLR4). RESULTS: In vivo, P. aeruginosa LPS induced robust osteolysis, and this effect was completely abrogated in mice lacking expression of TLR4. In vitro, P. aeruginosa LPS failed to induce development of osteoclasts directly in BMMs. However, P. aeruginosa LPS did stimulate osteoclastogenesis in BMM-osteoblast cocultures. CONCLUSIONS: P. aeruginosa LPS acts indirectly through osteoblasts to induce bone resorption. Optimal osteoclastogenesis in vitro required functional TLR4 expression in both BMMs and osteoblasts.

Original languageEnglish
Pages (from-to)841-847
Number of pages7
JournalLaryngoscope
Volume117
Issue number5
DOIs
StatePublished - May 2007

Keywords

  • Bone marrow monocyte (BMM)
  • Lipopolysaccharide (LPS)
  • Osteoblast
  • Osteoclast
  • Toll-like receptor 4 (TLR4)

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