Plasmid DNA-coding p62 as a bone effective anti-inflammatory/anabolic agent

Autor: Melania Capitani, Maria Giovanna Sabbieti, Antonio Concetti, Michael Y. Sherman, Vladimir L. Gabai, Franco M. Venanzi, Giuseppe Catone, Luigi Marchetti, Alexander M. Shneider, Cecilia Vullo, Dimitrios Agas, Victor Shifrin
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Scopus-Elsevier
Oncotarget
Popis: // Maria Giovanna Sabbieti 1, * , Dimitrios Agas 1, * , Melania Capitani 1 , Luigi Marchetti 1 , Antonio Concetti 1 , Cecilia Vullo 1 , Giuseppe Catone 1 , Vladimir Gabai 2 , Victor Shifrin 2 , Michael Y Sherman 3 , Alexander Shneider 2 , Franco M Venanzi 1 1 School of Biosciences and Veterinary Medicine, University of Camerino, Camerino (Italy) 2 CureLab Oncology Inc, 43 Rubury Hillway Needham MA (USA) 3 Dept. Biochem, Boston University School of Medicine, Boston MA (USA) * These authors have contributed equally to this work Correspondence to: Alexander Shneider, e-mail: ashneider@curelab.com Franco M Venanzi, e-mail: franco.venanzi@unicam.it Keywords: p62/SQSTM1, chronic inflammation, osteoporosis, immunotherapy Received: November 04, 2014 Accepted: December 09, 2014 Published: February 12, 2015 ABSTRACT We recently reported that a DNA plasmid coding p62-SQSTM1 acts as an effective anti tumor vaccine against both transplantable mouse tumors and canine spontaneous mammary neoplasms. Here we report the unexpected finding that intramuscular delivery of p62 DNA exerts a powerful anti-osteoporotic activity in a mouse model of inflammatory bone loss (i.e, ovariectomy) by combining bone-sparing and osteo-synthetic effects. Notably, the suppression of osteoporosis by p62DNA was associated with a sharp down-regulation of master inflammatory cytokines, and up-regulation of endogenous p62 protein by bone-marrow stromal cells. The present data provide a solid rational to apply p62 DNA vaccine as a safe, new therapeutic for treatment of inflammatory related bone loss diseases.
Databáze: OpenAIRE