Low-intensity pulsed ultrasound stimulation promotes osteoblast differentiation through hedgehog signaling

Kenichi Matsumoto, Tsuyoshi Shimo, Naito Kurio, Tatsuo Okui, Soichiro Ibaragi, Yuki Kunisada, Kyoichi Obata, Masanori Masui, Pang Pai, Yuu Horikiri, Nobuyuki Yamanaka, Masaharu Takigawa, Akira Sasaki

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Low-intensity pulsed ultrasound (LIPUS) has been used as an adjunct to fracture healing therapies, but the mechanisms underlying its action are not known. We reported that sonic hedgehog (SHH) signaling was activated in osteoblasts at the dynamic remodeling site of a bone fracture. Mechanical stimulation is a crucial factor in bone remodeling, and it is related to the primary cilia as a sensor of hedgehog signaling. Here we observed that LIPUS promoted callus formation in accord with Gli2-positive cells after 14 days at the mouse femur fractured site compared with a control group. An immunofluorescence analysis showed that the numbers of primary cilia and cilia/osterix double-positive osteoblasts were increased at the fracture site by LIPUS. LIPUS stimulated not only the number and the length of primary cilia, but also the levels of ciliated protein, Ift88 mRNA, and SHH, Gli1, and Gli2 in MC3T3-E1 cells. Further experiments revealed that LIPUS stimulated osteogenic differentiation in the presence of smoothened agonist (SAG) treatment. These results indicate that LIPUS stimulates osteogenic differentiation and the maturation of osteoblasts by a primary cilium-mediated activation of hedgehog signaling.

Original languageEnglish
Pages (from-to)4352-4360
Number of pages9
JournalJournal of Cellular Biochemistry
Volume119
Issue number6
DOIs
Publication statusPublished - Jun 2018

Keywords

  • LIPUS
  • fracture
  • osteoblast
  • primary cilia
  • sonic hedgehog

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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