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

质粒 DNA 编码 p62 作为骨骼有效的抗炎/合成代谢剂

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作者: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

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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