title: Direct Delivery of Recombinant Pin1 Protein Rescued Osteoblast Differentiation of Pin1-Deficient Cells.
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.
authors: Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Republic of Korea.
authors: Woo-Jin
authors: WJ
authors: Kim
authors: Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Republic of Korea.
authors: Rabia
authors: R
authors: Islam
authors: Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Republic of Korea.
authors: Bong-Soo
authors: BS
authors: Kim
authors: Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Republic of Korea.
authors: Young-Dan
authors: YD
authors: Cho
authors: Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Republic of Korea.
authors: Won-Joon
authors: WJ
authors: Yoon
authors: Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Republic of Korea.
authors: Jeong-Hwa
authors: JH
authors: Baek
authors: Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Republic of Korea.
authors: Kyung-Mi
authors: KM
authors: Woo
authors: Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Republic of Korea.
authors: Hyun-Mo
authors: HM
authors: Ryoo
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D005349:Fibroins / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology*; D053758:Nanoparticles; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology*; D010012:Osteogenesis / Q000187:drug effects*; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051898:Smad1 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism; D013997:Time Factors; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; D050659:Core Binding Factor Alpha 1 Subunit; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008055:Lipids; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C493716:Runx2 protein, mouse; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051902:Smad5 Protein; C497798:Smad5 protein, mouse; D051176:beta Catenin; D005349:Fibroins; C000606850:Pin1 protein, mouse