Induction of CXCL2 and CCL2 by pressure force requires IL-1β-MyD88 axis in osteoblasts

Aya Maeda, Kenjiro Bandow, Joji Kusuyama, Kyoko Kakimoto, Tomokazu Ohnishi, Shouichi Miyawaki, Tetsuya Matsuguchi

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Mechanical stresses including pressure force induce chemokine expressions in osteoblasts resulting in inflammatory reactions and bone remodeling. However, it has not been well elucidated how mechanical stresses induce inflammatory chemokine expressions in osteoblasts. IL-1β has been identified as an important pathogenic factor in bone loss diseases, such as inflammatory arthritis and periodontitis. Myeloid differentiation factor 88 (MyD88) is an essential downstream adaptor molecule of IL-1 receptor signaling. This study was to examine the gene expression profiles of inflammatory chemokines and the role of MyD88 in osteoblasts stimulated by pressure force. Pressure force (10g/cm2) induced significant mRNA increases of CXCL2, CCL2, and CCL5, as well as prompt phosphorylation of MAP kinases (ERK, p38 and JNK), in wild-type primary osteoblasts. The CXCL2 and CCL2 mRNA increases and MAP kinase phosphorylation were severely impaired in MyD88-/- osteoblasts. Constitutive low-level expression of IL-1β mRNA was similarly observed in both wild-type and MyD88-/- osteoblasts, which was not altered by pressure force stimulation. Notably, neutralization of IL-1β with a specific antibody significantly impaired pressure force-induced mRNA increases of CXCL2 and CCL2, as well as MAP kinase phosphorylation, in wild-type osteoblasts. Furthermore, pre-treatment with recombinant IL-1β significantly enhanced MAP kinase phosphorylation and mRNA increases of CXCL2 and CCL2 by pressure force in wild-type but not MyD88-/- osteoblasts. These results have suggested that the activation of MyD88 pathway by constitutive low-level IL-1β expression is essential for pressure force-induced CXCL2 and CCL2 expression in osteoblasts. Thus MyD88 signal in osteoblasts may be required for bone resorption by pressure force through chemokine induction.

Original languageEnglish
Pages (from-to)76-82
Number of pages7
JournalBone
Volume74
DOIs
Publication statusPublished - 2015 May 1
Externally publishedYes

Keywords

  • Chemokine
  • IL-1β
  • Mechanical stress
  • MyD88
  • Orthodontics
  • Osteoblasts

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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