Low-intensity pulsed ultrasound (LIPUS) inhibits LPS-induced inflammatory responses of osteoblasts through TLR4-MyD88 dissociation

Juna Nakao, Yasuyuki Fujii, Joji Kusuyama, Kenjiro Bandow, Kyoko Kakimoto, Tomokazu Ohnishi, Tetsuya Matsuguchi

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

Previous reports have shown that osteoblasts are mechano-sensitive. Low-intensity pulsed ultrasound (LIPUS) induces osteoblast differentiation and is an established therapy for bone fracture. Here we have examined how LIPUS affects inflammatory responses of osteoblasts to LPS. LPS rapidly induced mRNA expression of several chemokines including CCL2, CXCL1, and CXCL10 in both mouse osteoblast cell line and calvaria-derived osteoblasts. Simultaneous treatment by LIPUS significantly inhibited mRNA induction of CXCL1 and CXCL10 by LPS. LPS-induced phosphorylation of ERKs, p38 kinases, MEK1/2, MKK3/6, IKKs, TBK1, and Akt was decreased in LIPUS-treated osteoblasts. Furthermore, LIPUS inhibited the transcriptional activation of NF-κB responsive element and Interferon-sensitive response element (ISRE) by LPS. In a transient transfection experiment, LIPUS significantly inhibited TLR4-MyD88 complex formation. Thus LIPUS exerts anti-inflammatory effects on LPS-stimulated osteoblasts by inhibiting TLR4 signal transduction.

Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalBone
Volume58
DOIs
Publication statusPublished - 2014 Jan
Externally publishedYes

Keywords

  • Chemokines
  • Lipopolysaccharide (LPS)
  • Mechanotransduction
  • Osteoblasts
  • Toll-like receptors (TLR)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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