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SIRT1 is a positive regulator of in vivo bone mass and a therapeutic target for osteoporosis.

SIRT1 is a positive regulator of in vivo bone mass and a therapeutic target for osteoporosis.
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Zainabadi K, Liu CJ, Caldwell ALM, Guarente L,


Zainabadi K, Liu CJ, Caldwell ALM, Guarente L, (click to view)

Zainabadi K, Liu CJ, Caldwell ALM, Guarente L,

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PloS one 2017 09 2212(9) e0185236 doi 10.1371/journal.pone.0185236
Abstract

Overexpression or pharmacological activation of SIRT1 has been shown to extend the lifespan of mice and protect against aging-related diseases. Here we show that pharmacological activation of SIRT1 protects in two models of osteoporosis. Ovariectomized female mice and aged male mice, models for post-menopausal and aging-related osteoporosis, respectively, show significant improvements in bone mass upon treatment with SIRT1 agonist, SRT1720. Further, we find that calorie restriction (CR) results in a two-fold upregulation of sirt1 mRNA expression in bone tissue that is associated with increased bone mass in CR mice. Reciprocally, SIRT1 whole-body knockout (KO) mice, as well as osteoblast and osteoclast specific KOs, show a low bone mass phenotype; though double knockout mice (containing SIRT1 deleted in both osteoblasts and osteoclasts) do not show a more severe phenotype. Altogether, these findings provide strong evidence that SIRT1 is a positive regulator of bone mass and a promising target for the development of novel therapeutics for osteoporosis.

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