| First Author | Zainabadi K | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 9 | Pages | e0185236 |
| PubMed ID | 28937996 | Mgi Jnum | J:247291 |
| Mgi Id | MGI:5921752 | Doi | 10.1371/journal.pone.0185236 |
| Citation | Zainabadi K, et al. (2017) SIRT1 is a positive regulator of in vivo bone mass and a therapeutic target for osteoporosis. PLoS One 12(9):e0185236 |
| abstractText | 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. |
