Fak-Mapk, Hippo and Wnt signalling pathway expression and regulation in distraction osteogenesis

Cell Prolif. 2018 Aug;51(4):e12453. doi: 10.1111/cpr.12453. Epub 2018 Mar 5.

Abstract

Objectives: To investigate the mechanism of mechanical stimulation in bone formation and regeneration during distraction osteogenesis.

Materials and methods: In this study, microarray technology was used to investigate the time course of bone-related molecular changes in distraction osteogenesis in rats. Real-time PCR and Western-blot analyses were used to confirm the expression of genes identified in microarrays. Meanwhile, we used a lentivirus vector to inhibit Fak expression, in order to identify the osteogenic effect of Fak and Fak-Mapk pathway during distraction osteogenesis.

Results: Several components of the Wnt and Hippo pathways were found to be up- or down-regulated during distraction osteogenesis by microarray. Meanwhile, it was found that Fak, Src, Raf-1, Erk1, Jnk and p38-Mapk were up-regulated during gradual distraction, compared with consolidation. To further determine whether Fak-Mapk pathway played an important role in distraction osteogenesis, Fak was disrupted with a lentivirus vector. The expressions levels of p-Fak, p-Erk1/2, p-JNK and p-p38Mapk were decreased. Meanwhile, a poor early and late osteogenesis effect was found in the shRNA-Fak group.

Conclusion: It was inferred that the mechanical stimulus induces increased expression of Fak and activates Fak-Mapk pathway, by activation of Erk, Jnk and p38-Mapk pathway, and that Fak at least, in part, plays an important role in maintaining osteogenic effect by activating Fak-Mapk pathway during distraction osteogenesis.

MeSH terms

  • Animals
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology
  • Focal Adhesion Kinase 1 / antagonists & inhibitors
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism*
  • Hepatocyte Growth Factor / metabolism
  • MAP Kinase Signaling System / genetics*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Models, Animal
  • Osteogenesis, Distraction*
  • Proto-Oncogene Proteins / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Rats
  • Wnt Signaling Pathway / genetics*
  • Wnt4 Protein / genetics
  • Wnt4 Protein / metabolism
  • X-Ray Microtomography
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Wnt4 Protein
  • macrophage stimulating protein
  • Hepatocyte Growth Factor
  • Focal Adhesion Kinase 1
  • Ptk2 protein, rat
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases

Associated data

  • GENBANK/NM_199398
  • GENBANK/NM_053402
  • GENBANK/NM_001106321
  • GENBANK/NM_013025
  • GENBANK/NM_013081
  • GENBANK/NM_012639
  • GENBANK/NM_031977
  • GENBANK/NM_017347
  • GENBANK/NM_053829
  • GENBANK/NM_031020
  • GENBANK/NM_017008
  • GENBANK/NM_001108227
  • GENBANK/NM_001108111
  • GENBANK/NM_021266
  • GENBANK/NM_172035
  • GENBANK/NM_153305
  • GENBANK/XM_001072532
  • GENBANK/NM_001100700
  • GENBANK/NM_032080
  • GENBANK/NM_001106350
  • GENBANK/XM_001073458
  • GENBANK/NM_130429
  • GENBANK/NM_053357
  • GENBANK/NM_001107800
  • GENBANK/NM_01134543
  • GENBANK/NM_001034002
  • GENBANK/NM_001106243
  • GENBANK/NM_001106904
  • GENBANK/NM_001097581
  • GENBANK/NM_001033891