The sirtuin1 activator SRT3025 down-regulates sclerostin and rescues ovariectomy-induced bone loss and biomechanical deterioration in female mice

Endocrinology (United States)

Volumn 155, Issue 9, 2014, Pages 3508-3515

  Artsi, Hanna ^a   Cohen Kfir, Einav ^a,e   Gurt, Irina ^a   Shahar, Ron ^b   Bajayo, Alon ^b,f   Kalish, Noga ^b   Bellido, Teresita M ^c   Gabet, Yankel ^d   Dresner Pollak, Rivka ^a  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^b HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^c INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d TEL AVIV UNIVERSITY   (Israel)

^e HEBREW UNIVERSITY   (Israel)

^f UNIVERSITY OF COLORADO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME ACTIVATOR; PROCOLLAGEN; SCLEROSTIN; SRT 3025; UNCLASSIFIED DRUG; GLYCOPROTEIN; SIRTUIN 1; SOST PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOMECHANICS; BONE MASS; BONE TURNOVER; CONTROLLED STUDY; CORTICAL BONE; DETERIORATION; DOWN REGULATION; DRUG EFFECT; FEMALE; IN VITRO STUDY; MORPHOMETRICS; MOUSE; NONHUMAN; OSSIFICATION; OSTEOCYTE; OSTEOLYSIS; OVARIECTOMY-INDUCED OSTEOPOROSIS; PROTEIN EXPRESSION; TRABECULAR BONE; WNT SIGNALING PATHWAY; YOUNG MODULUS; ANIMAL; BONE DENSITY; C57BL MOUSE; ENZYMOLOGY; GENETICS; HUMAN; METABOLISM; OVARIECTOMY; PATHOPHYSIOLOGY; POSTMENOPAUSE OSTEOPOROSIS;

ANIMALS; BIOMECHANICAL PHENOMENA; BONE DENSITY; DOWN-REGULATION; ENZYME ACTIVATORS; FEMALE; GLYCOPROTEINS; HUMANS; MICE; MICE, INBRED C57BL; OSTEOPOROSIS, POSTMENOPAUSAL; OVARIECTOMY; SIRTUIN 1;

EID: 84907059211     PISSN: 00137227     EISSN: 19457170     Source Type: Journal    
DOI: 10.1210/en.2014-1334     Document Type: Article

References (40)

1. Riggs BL, Khosla S, Melton LJ 3rd. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. 2002;23:279-302.
2. Balemans W, Ebeling M, Patel N, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet. 2001;10:537-543.
3. Loots GG, Kneissel M, Keller H, et al. Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. Genome Res. 2005;15:928-935.
4. Li X, Ominsky MS, Niu QT, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res. 2008;23:860-869.
5. Winkler DG, Sutherland MK, Geoghegan JC, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003;22:6267-6276.
6. Li X, Ominsky MS, Warmington KS, et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2009; 24:578-588.
7. Ominsky MS, Vlasseros F, Jolette J, et al. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res. 2010;25: 948-959.
8. McClung MR, Grauer A, Boonen S, et al. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014;370:412-420.
9. Ke HZ, Richards WG, Li X, et al. Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev. 2012;33:747-783.
10. Mödder UI, Hoey KA, Amin S, et al. Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res. 2011;26:373-379.
11. Mödder UI, Roforth MM, Hoey K, et al. Effects of estrogen on osteoprogenitor cells and cytokines/bone-regulatory factors in postmenopausal women. Bone. 2011;49:202-207.
12. Fujita K, Roforth MM, Demaray S, et al. Effects of estrogen on bone mRNA levels of sclerostin and other genes relevant to bone metabolism in postmenopausal women. J Clin Endocrinol Metab. 2014; 99:E81-E88.
13. Haigis MC, Guarente LP. Mammalian sirtuins-emerging roles in physiology, aging, and calorie restriction. Genes Dev. 2006;20: 2913-2921.
14. Herranz D, Munoz-Martin M, Canamero M, et al. Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat Commun. 2010;1:3.
15. Edwards JR, Perrien DS, Fleming N, et al. Silent information regulator (Sir)T1 inhibits NF-KB signaling to maintain normal skeletal remodeling. J Bone Miner Res. 2013;28:960-969.
16. Cohen-Kfir E, Artsi H, Levin A, et al. Sirt1 is a regulator of bone mass and a repressor of Sost encoding for sclerostin, a bone formation inhibitor. Endocrinology. 2011;152:4514-4524.
17. Hubbard BP, Gomes AP, Dai H, et al. Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science. 2013; 339:1216-1219.
18. Milne JC, Lambert PD, Schenk S, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007;450:712-716.
19. Yao H, Chung S, Hwang JW, et al. SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice. J Clin Invest. 2012;122:2032-2045.
20. Ichikawa T, Hayashi R, Suzuki K, et al. Sirtuin 1 activator SRT1720 suppresses inflammation in an ovalbumin-induced mouse model of asthma. Respirology. 2013;18:332-339.
21. Tong C, Morrison A, Mattison S, et al. Impaired SIRT1 nucleocy-toplasmic shuttling in the senescent heart during ischemic stress. FASEB J. 2013;27:4332-4342.
22. Shindler KS, Ventura E, Dutt M, Elliott P, Fitzgerald DC, Rostami A. Oral resveratrol reduces neuronal damage in a model of multiple sclerosis. J Neuroophthalmol. 2010;30:328-339.
23. Hubbard BP, Sinclair DA. Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol Sci. 2014;35:146-154.
24. Simsa-Maziel S, Zaretsky J, Reich A, Koren Y, Shahar R, Monso-nego-Ornan E. IL-1RI participates in normal growth plate development and bone modeling. Am J Physiol Endocrinol Metab. 305: E15-E21.
25. Bellido T, Ali AA, Plotkin LI, et al. Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem. 2003; 278:50259-50272.
26. Hildebrand T, Rüegsegger P. Quantification of bone microarchitecture with the structure model index. Comput Methods Biomech Biomed Engin. 1997;1:15-23.
27. Dallas SL, Prideaux M, Bonewald LF. The osteocyte: an endocrine cell.. and more. Endocr Rev. 2013;34:658-690.
28. Gertz M, Fischer F, Nguyen GT, et al. Ex-527 inhibits Sirtuins by exploiting their unique NAD +-dependent deacetylation mechanism. Proc Natl Acad Sci USA. 2013;110:E2772-E2781.
29. Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med. 2013;19:179-192.
30. Hodsman AB, Bauer DC, Dempster DW, et al. Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocr Rev. 2005; 26:688-703.
31. Lindsay R, Zhou H, Cosman F, Nieves J, Dempster DW, Hodsman AB. Effects of a one-month treatment with PTH(1-34) on bone formation on cancellous, endocortical, and periosteal surfaces of the human ilium. J Bone Miner Res. 2007;22:495-502.
32. Hamann C, Kirschner S, Günther KP, Hofbauer LC. Bone, sweet bone[mdash]osteoporotic fractures in diabetes mellitus. Nat Rev Endocrinol. 2012;8:297-305.
33. García-Martín A, Rozas-Moreno P, Reyes-García R, et al. Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2012;97:234-241.
34. Hie M, Iitsuka N, Otsuka T, Tsukamoto I. Insulin-dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation. Int J Mol Med. 2011;28: 455-462.
35. Hamann C, Rauner M, Höhna Y, et al. Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with type 2 diabetes mellitus. J Bone Miner Res. 2013; 28:627-638.
36. Nuche-Berenguer B, Moreno P, Portal-Nuñez S, Dapía S, Esbrit P, Villanueva-Peñacarrillo ML. Exendin-4 exerts osteogenic actions in insulin-resistant and type 2 diabetic states. Regul Pept. 2010;159: 61-66.
37. Elbaz A, Rivas D, Duque G. Effect of estrogens on bone marrow adipogenesis and Sirt1 in aging C57BL/6J mice. Biogerontology. 2009;10:747-755.
38. Zhang J, Lazarenko OP, Blackburn ML, Badger TM, Ronis MJ, Chen JR. Blueberry consumption prevents loss of collagen in bone matrix and inhibits senescence pathways in osteoblastic cells. Age (Dordr). 2013;35:807-820.
39. Elangovan S, Ramachandran S, Venkatesan N, et al. SIRT1 is essential for oncogenic signaling by estrogen/estrogen receptor a in breast cancer. Cancer Res. 2011;71:6654-6664.
40. Chen Y, Zhao W, Yang JS, et al. Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways. Mol Cell Proteomics. 2012;11:1048-1062.