TY - JOUR
T1 - Low-intensity pulsed ultrasound (LIPUS) inhibits LPS-induced inflammatory responses of osteoblasts through TLR4-MyD88 dissociation
AU - Nakao, Juna
AU - Fujii, Yasuyuki
AU - Kusuyama, Joji
AU - Bandow, Kenjiro
AU - Kakimoto, Kyoko
AU - Ohnishi, Tomokazu
AU - Matsuguchi, Tetsuya
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
KW - Chemokines
KW - Lipopolysaccharide (LPS)
KW - Mechanotransduction
KW - Osteoblasts
KW - Toll-like receptors (TLR)
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UR - http://www.scopus.com/inward/citedby.url?scp=84886304007&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2013.09.018
DO - 10.1016/j.bone.2013.09.018
M3 - Article
C2 - 24091132
AN - SCOPUS:84886304007
SN - 8756-3282
VL - 58
SP - 17
EP - 25
JO - Bone
JF - Bone
ER -
