@article {10154,
	title = {The Sirtuin1 Activator SRT3025 Down-Regulates Sclerostin and Rescues Ovariectomy-Induced Bone Loss and Biomechanical Deterioration in Female Mice},
	journal = {JOURNAL OF BONE AND MINERAL RESEARCH},
	volume = {29},
	year = {2014},
	pages = {S403-S403},
	abstract = {Estrogen deficiency leads to rapid bone loss and skeletal fragility. Sclerostin, encoded by the sost gene,and a product of the osteocyte, is a negative regulator of bone formation. Blocking sclerostin increasesbone mass and strength in animals and humans. Sirtuin1 (Sirt1), a player in aging and metabolism,regulates bone mass and inhibits sost expression by deacetylating histone 3 at its promoter.Weaskedwhether a Sirt1-activating compound could rescue ovariectomy (OVX)-induced bone loss and biomechanicaldeterioration in 9-week-old C57BL/6 mice. OVX resulted in a substantial decrease in skeletalSirt1 expression accompanied by an increase in sclerostin. Oral administration of SRT3025, a Sirt1activator, at 50 and 100 mg/kgd for 6 weeks starting 6 weeks after OVX fully reversed the deleteriouseffects of OVX on vertebral bone mass, microarchitecture, and femoral biomechanical properties.Treatment with SRT3025 decreased bone sclerostin expression and increased cortical periosteal mineralizingsurface and serum propeptide of type I procollagen, a bone formation marker. In vitro, in themurinelongboneosteocyte-Y4 osteocyte-like cell lineSRT3025down-regulated sclerostinandinactive-catenin, whereas a reciprocal effect was observed with EX-527, a Sirt1 inhibitor. Sirt1 activation bySirt1-activating compounds is a potential novel pathway to down-regulate sclerostin and design anabolictherapies for osteoporosis concurrently ameliorating other metabolic and age-associatedconditions. (Endocrinology 155: 3508{\textendash}3515, 2014)},
	author = {Artsi, Hanna and Cohen-Kfir, Einav and Gurt, Irina and Ron Shahar and Bajayo, Alon and Kalish, Noga and Bellido, Teresita and Gabet, Yankel and Dresner-Pollak, Rivka}
}
