FAK and BMP-9 synergistically trigger osteogenic differentiation and bone formation of adipose derived stem cells through enhancing Wnt-β-catenin signaling

Biomed Pharmacother. 2018 Sep:105:753-757. doi: 10.1016/j.biopha.2018.04.185. Epub 2018 Jun 14.

Abstract

Backgrounds: Adipose derived stem cells (ADSCs) could undergo osteogenesis via focal adhesion kinase (FAK) and bone morphogenetic protein (BMP) 9 signals, both of which could affect Wnt-β-catenin signal, a signal pathway closely related to ADSCs osteogenesis. It's still enigma whether FAK and BMP-9 contribute to osteogenesis. Here, we examined the effect of FAK on BMP9-inducedosteogenic differentiation, unveiled the possible molecular mechanism underling this process.

Methods: In the present study, ADSCs were isolated and purified, and cells of passage 3 underwent virus mediated transfection to prepare ADSCs with stable FAK shRNA expression. Cell viability and migration were detected by MTT and transwell assay, respectively. Expression of osteogenic gene, phosphorylation of FAK and GSK were detected by western blot. Osteogenic potential was evaluated by activity of alkaline phosphatase (ALP) and calcium deposition by ALP staining and Alizarin Red S staining.

Results: BMP-9 administration promoted ADSCs osteogenesis. Knocking down FAK attenuated this process, inhibited osteogenic proteins expression through Wnt-β-catenin signal. BMP-9 also triggered ADSCs proliferation and migration, and shFAK antagonized such effects too. Although Wnt signal is affected by FAK shRNA, Smad signal remains intact in ADSCs with shFAK.

Conclusion: FAK and BMP-9 could cross talk on Wnt signal pathway and promote ADSCs osteogenesis. FAK could participate in BMP-9 induced ADSCs osteogenesis via Wnt signal pathway other than Smads signals (see in graph).

Keywords: BMP-9; FAK; Osteogenesis; Stem cell; Wnt; β-catenin.

MeSH terms

  • Adipose Tissue / cytology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism*
  • Gene Knockdown Techniques
  • Growth Differentiation Factor 2
  • Growth Differentiation Factors / metabolism*
  • Growth Differentiation Factors / pharmacology
  • Humans
  • Osteogenesis / physiology*
  • Phosphorylation
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Wnt Signaling Pathway* / drug effects

Substances

  • GDF2 protein, human
  • Growth Differentiation Factor 2
  • Growth Differentiation Factors
  • Focal Adhesion Kinase 1
  • PTK2 protein, human