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

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

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

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 osteosynthetic 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.

Original language	English
Pages (from-to)	3590-3599
Number of pages	10
Journal	Oncotarget
Volume	6
Issue number	6
DOIs	https://doi.org/10.18632/oncotarget.2884
State	Published - 2015
Externally published	Yes

Keywords

Chronic inflammation
Immunotherapy
Osteoporosis
p62/SQSTM1

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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 osteosynthetic 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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AU - Sabbieti, Maria Giovanna

AU - Agas, Dimitrios

AU - Capitani, Melania

AU - Marchetti, Luigi

AU - Concetti, Antonio

AU - Vullo, Cecilia

AU - Catone, Giuseppe

AU - Gabai, Vladimir

AU - Shifrin, Victor

AU - Sherman, Michael Y.

AU - Shneider, Alexander

AU - Venanzi, Franco M.

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

Abstract

Keywords

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