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

Maria Giovanna Sabbieti; Dimitrios Agas; Melania Capitani; Luigi Marchetti; Antonio Concetti; Cecilia Vullo; Giuseppe Catone; Vladimir Gabai; Victor Shifrin; Michael Y. Sherman; Alexander Shneider; Franco M. Venanzi

doi:10.18632/oncotarget.2884

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Research Papers: Gerotarget (Focus on Aging):

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

Maria Giovanna Sabbieti _, Dimitrios Agas, Melania Capitani, Luigi Marchetti, Antonio Concetti, Cecilia Vullo, Giuseppe Catone, Vladimir Gabai, Victor Shifrin, Michael Y. Sherman, Alexander Shneider and Franco M. Venanzi

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Oncotarget. 2015; 6:3590-3599. https://doi.org/10.18632/oncotarget.2884

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Abstract

Maria Giovanna Sabbieti1,*, Dimitrios Agas1,*, Melania Capitani1, Luigi Marchetti1, Antonio Concetti1, Cecilia Vullo1, Giuseppe Catone1, Vladimir Gabai2, Victor Shifrin2, Michael Y Sherman3, Alexander Shneider2, Franco M Venanzi1

1School of Biosciences and Veterinary Medicine, University of Camerino, Camerino (Italy)

2CureLab Oncology Inc, 43 Rubury Hillway Needham MA (USA)

3Dept. Biochem, Boston University School of Medicine, Boston MA (USA)

*These authors have contributed equally to this work

Correspondence to:

Alexander Shneider, e-mail: [email protected]

Franco M Venanzi, e-mail: [email protected]

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.

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Research Papers: Gerotarget (Focus on Aging):

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

Abstract