Sonic Hedgehog Regulates Osteoblast Function by Focal Adhesion Kinase Signaling in the Process of Fracture Healing

Yuu Horikiri, Tsuyoshi Shimo, Naito Kurio, Tatsuo Okui, Kenichi Matsumoto, Masahiro Iwamoto, Akira Sasaki

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Several biological studies have indicated that hedgehog signaling plays an important role in osteoblast proliferation and differentiation, and sonic hedgehog (SHH) expression is positively correlated with phosphorylated focal adhesion kinase (FAK) Tyr397. However, the relationship between them and their role in the process of normal fracture repair has not been clarified yet. Immunohistochemical analysis revealed that SHH and pFAK Tyr397 were expressed in bone marrow cells and that pFAK Tyr397 was also detected in ALP-positive osteoblasts near the TRAP-positive osteoclasts in the fracture site in the ribs of mice on day 5 after fracture. SHH and pFAK Tyr397 were detectable in osteoblasts near the hypertrophic chondrocytes on day 14. In vitro analysis showed that SHH up-regulated the expression of FAK mRNA and pFAK Tyr397 time dependently in osteoblastic MC3T3-E1 cells. Functional analysis revealed that 5 lentivirus encoding short hairpin FAK RNAs (shFAK)-infected MC3T3-E1 cell groups displayed a round morphology and decreased proliferation, adhesion, migration, and differentiation. SHH stimulated the proliferation and differentiation of MC3T3-E1 cells, but had no effect on the shFAK-infected cells. SHH also stimulated osteoclast formation in a co-culture system containing MC3T3-E1 and murine CD11b+ bone marrow cells, but did not affect the shFAK-infected MC3T3-E1 co-culture group. These data suggest that SHH signaling was activated in osteoblasts at the dynamic remodeling site of a bone fracture and regulated their proliferation and differentiation, as well as osteoclast formation, via FAK signaling.

Original languageEnglish
Article numbere76785
JournalPLoS One
Volume8
Issue number10
DOIs
Publication statusPublished - Oct 4 2013

Fingerprint

non-specific protein-tyrosine kinase
Focal Adhesion Protein-Tyrosine Kinases
Fracture Healing
Hedgehogs
Erinaceidae
osteoblasts
Osteoblasts
Bone
RNA
osteoclasts
Osteoclasts
Cells
Functional analysis
bone marrow cells
coculture
small interfering RNA
Coculture Techniques
Bone Marrow Cells
Small Interfering RNA
Repair

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sonic Hedgehog Regulates Osteoblast Function by Focal Adhesion Kinase Signaling in the Process of Fracture Healing. / Horikiri, Yuu; Shimo, Tsuyoshi; Kurio, Naito; Okui, Tatsuo; Matsumoto, Kenichi; Iwamoto, Masahiro; Sasaki, Akira.

In: PLoS One, Vol. 8, No. 10, e76785, 04.10.2013.

Research output: Contribution to journalArticle

Horikiri, Yuu ; Shimo, Tsuyoshi ; Kurio, Naito ; Okui, Tatsuo ; Matsumoto, Kenichi ; Iwamoto, Masahiro ; Sasaki, Akira. / Sonic Hedgehog Regulates Osteoblast Function by Focal Adhesion Kinase Signaling in the Process of Fracture Healing. In: PLoS One. 2013 ; Vol. 8, No. 10.
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