Direct Delivery of Recombinant Pin1 Protein Rescued Osteoblast Differentiation of Pin1-Deficient Cells

J Cell Physiol. 2017 Oct;232(10):2798-2805. doi: 10.1002/jcp.25673. Epub 2017 May 5.

Abstract

Pin1 is a peptidyl prolyl cis-trans isomerase that specifically binds to the phosphoserine-proline or phosphothreonine-proline motifs of several proteins. We reported that Pin1 plays a critical role in the fate determination of Smad1/5, Runx2, and β-catenin that are indispensable nuclear proteins for osteoblast differentiation. Though several chemical inhibitors has been discovered for Pin1, no activator has been reported as of yet. In this study, we directly introduced recombinant Pin1 protein successfully into the cytoplasm via fibroin nanoparticle encapsulated in cationic lipid. This nanoparticle-lipid complex delivered its cargo with a high efficiency and a low cytotoxicity. Direct delivery of Pin1 leads to increased Runx2 and Smad signaling and resulted in recovery of the osteogenic marker genes expression and the deposition of mineral in Pin1-deficient cells. These result indicated that a direct Pin1 protein delivery method could be a potential therapeutics for the osteopenic diseases. J. Cell. Physiol. 232: 2798-2805, 2017. © 2016 Wiley Periodicals, Inc.

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Differentiation / drug effects*
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Drug Carriers
  • Drug Compounding
  • Fibroins / chemistry
  • Lipids / chemistry
  • Male
  • Mice
  • Mice, Knockout
  • NIMA-Interacting Peptidylprolyl Isomerase / deficiency*
  • NIMA-Interacting Peptidylprolyl Isomerase / genetics
  • NIMA-Interacting Peptidylprolyl Isomerase / pharmacology*
  • Nanoparticles
  • Osteoblasts / drug effects*
  • Osteoblasts / enzymology*
  • Osteogenesis / drug effects*
  • Phenotype
  • Recombinant Fusion Proteins / pharmacology*
  • Recombinant Proteins / pharmacology
  • Signal Transduction / drug effects
  • Smad1 Protein / metabolism
  • Smad5 Protein / metabolism
  • Time Factors
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, mouse
  • Core Binding Factor Alpha 1 Subunit
  • Delayed-Action Preparations
  • Drug Carriers
  • Lipids
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Runx2 protein, mouse
  • Smad1 Protein
  • Smad1 protein, mouse
  • Smad5 Protein
  • Smad5 protein, mouse
  • beta Catenin
  • Fibroins
  • Pin1 protein, mouse