Methylation of bone SOST, its mRNA, and serum sclerostin levels correlate strongly with fracture risk in postmenopausal women

Journal of Bone and Mineral Research

Volumn 30, Issue 2, 2015, Pages 249-256

  Reppe, Sjur ^a,b,c   Noer, Agate ^a   Grimholt, Runa M ^a   Halldórsson, Bjarni V ^d   Medina Gomez, Carolina ^e   Gautvik, Vigdis T ^c   Olstad, Ole Kristoffer ^a   Berg, Jens Petter ^a,c   Datta, Harish ^f   Estrada, Karol ^g   Hofman, Albert ^e   Uitterlinden, André G ^e   Rivadeneira, Fernando ^e   Lyle, Robert ^a,c   Collas, Philippe ^c   Gautvik, Kaare M ^a,b,c  

^a OSLO UNIVERSITY HOSPITAL   (Norway)

^b LOVISENBERG DIAKONALE HOSPITAL   (Norway)

^c UNIVERSITY OF OSLO   (Norway)

^d REYKJAVIK UNIVERSITY   (Iceland)

^e ERASMUS MEDICAL CENTER   (Netherlands)

^f NEWCASTLE UNIVERSITY   (United Kingdom)

^g MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Diseases and disorders of related to bone; Epigenetics; Genetic research; Human association studies; Osteoporosis

Indexed keywords

ALKALINE PHOSPHATASE; BIOLOGICAL MARKER; COLLAGEN; DNA; MESSENGER RNA; SCLEROSTIN; BONE MORPHOGENETIC PROTEIN; GENETIC MARKER; SOST PROTEIN, HUMAN;

ADULT; AGE; AGED; ARTICLE; BODY MASS; BONE BIOPSY; BONE REMODELING; BONE TURNOVER; COLLAGEN DEGRADATION; CONTROLLED STUDY; CPG ISLAND; DNA METHYLATION; EPIGENETICS; FEMALE; GENE; GENE EXPRESSION; GENE IDENTIFICATION; GENE REPLICATION; GENETIC ASSOCIATION; GENETIC RISK; HIP FRACTURE; HUMAN; HUMAN TISSUE; ILIAC CREST; NORWEGIAN (PEOPLE); OSTEOPOROSIS; POSTMENOPAUSE; PROMOTER REGION; PROTEIN BLOOD LEVEL; SINGLE NUCLEOTIDE POLYMORPHISM; SOST GENE; TRANSCRIPTION INITIATION SITE; BLOOD; BONE; BONE DENSITY; DEMOGRAPHY; FRACTURE; GENETIC MARKER; GENETICS; METABOLISM; METHYLATION; MIDDLE AGED; PATHOLOGY; POSTMENOPAUSE OSTEOPOROSIS; RISK FACTOR; URINE; VERY ELDERLY;

AGED; AGED, 80 AND OVER; BIOMARKERS; BONE AND BONES; BONE DENSITY; BONE MORPHOGENETIC PROTEINS; DEMOGRAPHY; FEMALE; FRACTURES, BONE; GENETIC MARKERS; HUMANS; METHYLATION; MIDDLE AGED; OSTEOPOROSIS, POSTMENOPAUSAL; POLYMORPHISM, SINGLE NUCLEOTIDE; POSTMENOPAUSE; RISK FACTORS; RNA, MESSENGER;

EID: 84921773267     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.2342     Document Type: Article

References (40)

1. Ke HZ, Richards WG, Li X, Ominsky MS. Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev. 2012;33(5):747-83.
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(5):537-43.
3. Balemans W, Patel N, Ebeling M, et al. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet. 2002;39(2):91-7.
4. Brunkow ME, Gardner JC, Van Ness J, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001;68(3):577-89.
5. Staehling-Hampton K, Proll S, Paeper BW, et al. A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet. 2002;110(2):144-52.
6. 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(6):860-9.
7. He X, Saint-Jeannet JP, Wang Y, Nathans J, Dawid I, Varmus H. A member of the Frizzled protein family mediating axis induction by Wnt-5A. Science. 1997;275(5306):1652-54.
8. Bhat RA, Stauffer B, Della PA, Bodine PV. Wnt3-frizzled 1 chimera as a model to study canonical Wnt signaling. J Cell Biochem. 2010;109(5):876-84.
9. Anastasilakis AD, Polyzos SA, Toulis KA. Role of wingless tail signaling pathway in osteoporosis: an update of current knowledge. Curr Opin Endocrinol Diabetes Obes. 2011;18(6):383-8.
10. Monroe DG, McGee-Lawrence ME, Oursler MJ, Westendorf JJ. Update on Wnt signaling in bone cell biology and bone disease. Gene. 2011;492(1):1-18.
11. Gaudio A, Pennisi P, Bratengeier C, et al. Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab. 2010;95(5):2248-53.
12. Garnero P, Sornay-Rendu E, Munoz F, Borel O, Chapurlat RD. Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study. Osteoporos Int. 2013 Feb;24(2):489-94.
13. Modder 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(2):373-9.
14. Polyzos SA, Anastasilakis AD, Bratengeier C, Woloszczuk W, Papatheodorou A, Terpos E. Serum sclerostin levels positively correlate with lumbar spinal bone mineral density in postmenopausal women-the six-month effect of risedronate and teriparatide. Osteoporos Int. 2012 Mar;23(3):1171-6.
15. Arasu A, Cawthon PM, Lui LY, et al. Serum sclerostin and risk of hip fracture in older Caucasian women. J Clin Endocrinol Metab. 2012;97(6):2027-32.
16. Dovjak P, Foger-Samwald U, Dorfer S, Pietschmann P, Kudlacek S, Kapfenberger A. Serum levels of sclerostin and dickkopf-1 in geriatric patients with osteoporotic hip fractures. J Bone Miner Res. 2013;28(Suppl 1):279.
17. Estrada K, Styrkarsdottir U, Evangelou E, et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. 2012;44(5):491-501.
18. Reppe S, Refvem H, Gautvik VT, et al. Eight genes are highly associated with BMD variation in postmenopausal Caucasian women. Bone. 2010;46(3):604-12.
19. Noer A, Sorensen AL, Boquest AC, Collas P. Stable CpG hypomethylation of adipogenic promoters in freshly isolated, cultured, and differentiated mesenchymal stem cells from adipose tissue. Mol Biol Cell. 2006;17(8):3543-56.
20. Aryee MJ, Jaffe AE, Corrada-Bravo H, et al. Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014;30(10):1363-9.
21. Teschendorff AE1, Marabita F, Lechner M, et al. A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data. Bioinformatics. 2013;29(2):189-96.
22. Jemtland R, Holden M, Reppe S, et al. Molecular disease map of bone characterizing the postmenopausal osteoporosis phenotype. J Bone Miner Res. 2011;26(8):1793-801.
23. Hofman A, van Duijn CM, Franco OH, et al. The Rotterdam Study: 2012 objectives and design update. Eur J Epidemiol. 2011;26(8):657-86.
24. Estrada K, Abuseiris A, Grosveld FG, Uitterlinden AG, Knoch TA, Rivadeneira F. GRIMP: a web- and grid-based tool for high-speed analysis of large-scale genome-wide association using imputed data. Bioinformatics. 2009;25(20):2750-2.
25. Sevetson B, Taylor S, Pan Y. Cbfa1/RUNX2 directs specific expression of the sclerosteosis gene (SOST). J Biol Chem. 2004;279(14):13849-58.
26. Huang QY, Li GH, Kung AW. The -9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPalpha and FOXA1 binding is associated with osteoporosis. Bone. 2009;45(2):289-94.
27. Bonewald LF. Osteocytes as dynamic multifunctional cells. Ann N Y Acad Sci. 2007;1116:281-90.
28. Truong L, Fazzalari J, Kuliwaba J. Osteocyte apoptosis and expression of sclerostin in postmenopausal women with fragility hip fracture. J Bone Miner Res. 2009;34(Suppl 1):SU0260.
29. Delgado-Calle J, Arozamena J, Garća-Renedo R, et al. Osteocyte deficiency in hip fractures. Calcif Tissue Int. 2011;89(4):327-34.
30. Ardawi MS, Rouzi AA, Al-Sibiani SA, Al-Senani NS, Qari MH, Mousa SA. High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: the Center of Excellence for Osteoporosis Research Study. J Bone Miner Res. 2012;27(12):2592-602.
31. Amrein K, Dobnig H, Wagner D, et al. Sclerostin in institutionalized elderly women: associations with quantitative bone ultrasound, bone turnover, fractures, and mortality. J Am Geriatr Soc. 2014;62:1023-9.
32. Dawson-Hughes B, Harris SS, Ceglia L, Palermo NJ. Serum sclerostin levels vary with season. J Clin Endocrinol Metab. 2014;99(1):E149-52.
33. Varanasi SS, Olstad OK, Swan DC, et al. Skeletal site-related variation in human trabecular bone transcriptome and signaling. PLoS One. 2010;5(5):e10692.
34. Ardawi MS, Al-Kadi HA, Rouzi AA, Qari MH. Determinants of serum sclerostin in healthy pre- and postmenopausal women. J Bone Miner Res. 2011;26(12):2812-22.
35. Delgado-Calle J, Riancho JA, Klein-Nulend J. Nitric oxide is involved in the down-regulation of SOST expression induced by mechanical loading. Calcif Tissue Int. 2014;94(4):414-22.
36. Hsieh CL. Dependence of transcriptional repression on CpG methylation density. Mol Cell Biol. 1994;14(8):5487-94.
37. Delgado-Calle J, Sanudo C, Bolado A, et al. DNA methylation contributes to the regulation of sclerostin expression in human osteocytes. J Bone Miner Res. 2012;27(4):926-37.
38. Harvey NC, Sheppard A, Godfrey KM, et al. Childhood bone mineral content is associated with methylation status of the RXRA promoter at birth. J Bone Miner Res. 2014;29(3):600-7.
39. Harvey NC, Lillycrop KA, Garratt E, et al. Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content. Calcif Tissue Int. 2012;90(2):120-7.
40. Hannum G, Guinney J, Zhao L, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013;49(2):359-67.