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.

Highlights

  • The adapter protein p62 is a multifunctional molecule involved in a myriad of cellular processes that modulate proliferation, cell death, inflammation and immune res­ ponse [1]

  • 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

  • We demonstrated that p62 DNA plasmid when administered in neo-adjuvant setting decreased and/or stabilized growth of advanced lesions in canine mammary tumors [7]

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Summary

Introduction

The adapter protein p62 ( known as seq­ uestosome1/SQSTM1) is a multifunctional molecule involved in a myriad of cellular processes that modulate proliferation, cell death, inflammation and immune res­ ponse [1]. 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. 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.

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