MULTIFACTORIAL PATHOGENESIS OF OSTEOPOROSIS AND THE ROLE OF GENES OF CANONICAL WNT-SIGNALING PATHWAY
Abstract
Nowadays, multifactorial nature of osteoporosis does not raise any doubts. Besides, it should be noted that about 90% disease cases are determined genetically. In 1990-s a number of candidate genes mutations were established which increase the risk of osteoporosis development. VDR, ESR1, ESR2, COLIA1, PTH, CT, CTR, BGP, AR, GCCR, TGFB1, IL-6, IGF1, IL-1ra, OPG were considered to be this kind of genes. New genetic analysis technologies (GWAS, etc.) gave the opportunity to expand our conception about multi genomic pathogenesis of osteoporosis and to point out a new group of genes candidate - a canonical Wnt-signaling pathway genes (CTNNB1, SOST, FOXC2, FOXL1, LRP4, LRP5, WNT1, WNT3, WNT16, DKK1, AXIN1, JAG1, etc.). Extreme importance of canonical Wnt-signaling pathway and genes given above in skeleton formation and its strength necessitate the need for further scientific research and opens perspective to improve osteoporosis diagnostics, treatment and prognosis.
References
1. Баранов B.C. Генетический паспорт - основа индивидуальной и предиктивной медицины. СПб., 2009. 528 с.
2. Казимирко В.К., Коваленко В.Н., Флегонтова В.В. Инволюционный остеоартроз и остеопороз. Донецк, 2011. 724 с.
3. Поворознюк В.В., Плудовски П., Балацкая Н.И., Муц В.Я., Климовицкий Ф.В., Резниченко Н.А., Синий О.В., Майлян Э.А., Панькив И.В. Дефицит и недостаточность витамина D: эпидемиология, диагностика, профилактика и лечение. Киев, 2015. 262 с.
4. Поворознюк В.В., Резниченко Н.А., Майлян Э.А. Иммунологические аспекты постменопаузального остеопороза. Боль. Суставы. Позвоночник. 2013; 3: 21-26.
5. Поворознюк В.В., Резниченко Н.А., Майлян Э.А. Регуляция эстрогенами ремоделирования костной ткани. Репродуктивная эндокринология. 2014; 1: 14-18.
6. Canto-Cetina T., Polanco Reyes L., Gonzalez Herrera L., Rojano-Mejia D., Coral-Vazquez R.M., Coronel A., Canto P. Polymorphism of LRP5, but not of TNFRSF11B, is associated with a decrease in bone mineral density in postmenopausal Maya-Mestizo women. Am. J. Hum. Biol. 2013; 25(6): 713-718.
7. Durmaz A.A., Karaca E., Demkow U., Toruner G., Schoumans J., Cogulu O. Evolution of Genetic Techniques: Past, Present, and Beyond. Biomed. Res. Int. 2015; 2015: 461524.
8. Fahiminiya S., Majewski J., Mort J., Moffatt P., Glorieux F.H., Rauch F. Mutations in WNT1 are a cause of osteogenesis imperfecta. J. Med. Genet. 2013; 50(5): 345-348.
9. Feng X., McDonald J.M. Disorders of Bone Remodeling. Annu. Rev. Pathol. 2011; 6: 121-145.
10. Garcia-Ibarbia C., Pérez-Nünez M.I., Olmos J.M., Valero C., Pérez-Aguilar M.D., Hernandez J.L., Zarrabeitia M.T., Gonzalez-Macias J., Riancho J.A. Missense polymorphisms of the WNT16 gene are associated with bone mass, hip geometry and fractures. Osteoporos. Int. 2013; 24(9): 2449-2454.
11. Hsu Y.H., Kiel D.P Clinical review: Genome-wide association studies of skeletal phenotypes: what we have learned and where we are headed. J Clin. Endocrinol. Metab. 2012; 97(10): 1958-1977.
12. Issack P.S., Helfet D.L., Lane J.M. Role of Wnt Signaling in Bone Remodeling and Repair. HSS J. 2008; 4(1): 66-70.
13. Johnson M.L., Lara N., Kamel M.A. How genomics has informed our understanding of the pathogenesis of osteoporosis. Genome Med. 2009; 1(9): 84.
14. Kung A.W., Xiao S.M., Cherny S., Li G.H., Gao Y., Tso G., Lau K.S., Luk K.D., Liu J.M., Cui B., Zhang M.J., Zhang Z.L., He J.W., Yue H., Xia W.B., Luo L.M., He S.L., Kiel D.P., Karasik D., Hsu Y.H., Cupples L.A., Demissie S., Styrkarsdottir U., Halldorsson B.V., Sigurdsson G., Thorsteinsdottir U., Stefansson K., Richards J.B., Zhai G., Soranzo N., Valdes A., Spector T.D., Sham P.C. Association of JAG1 with bone mineral density and osteoporotic fractures: a genome-wide association study and follow-up replication studies. Am. J. Hum. Genet. 2010; 86(2): 229-239.
15. Laine C.M., Joeng K.S., Campeau P.M., Kiviranta R., Tarkkonen K., Grover M., Lu J.T., Pekkinen M., Wessman M., Heino T.J., Nieminen-Pihala V., Aronen M., Laine T., Kröger H., Cole W. G., Lehesjoki A.E., Nevarez L., Krakow D., Curry C.J., Cohn D.H., Gibbs R.A., Lee B.H., Mäkitie O. WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta. N. Engl. J. Med. 2013; 368(19): 1809-1816.
16. Lee Y.H., Woo J.H., Choi S.J., Ji J.D., Song G.G. Association between the A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene and bone mineral density: a metaanalysis. Rheumatol. Int. 2009; 29(5): 539-544.
17. Liu Y.Z., Liu Y.J., Recker R.R., Deng H.W. Molecular studies of identification of genes for osteoporosis: the 2002 update. J. Endocrinol. 2003; 177(2): 147-196.
18. Markatseli A.E., Hatzi E., Bouba I., Georgiou I., Challa A., Tigas S., Tsatsoulis A. Association of the A1330V and V667M polymorphisms of LRP5 with bone mineral density in Greek peri- and postmenopausal women. Maturitas. 2011; 70(2): 188-193.
19. Medina-Gomez C., Kemp J.P., Estrada K., Eriksson J., Liu J., Reppe S., Evans D.M., Heppe D.H., Vandenput L., Herrera L., Ring S.M., Kruithof C.J., Timpson N.J., Zillikens M.C., Olstad O.K., Zheng H.F., Richards J.B., St Pourcain B., Hofman A., Jaddoe V.W., Smith G.D., Lorentzon M., Gautvik K.M., Uitterlinden A.G., Brommage R., Ohlsson C., Tobias J.H., Rivadeneira F. Meta-analysis of genome-wide scans for total body BMD in children and adults reveals allelic heterogeneity and age-specific effects at the WNT16 locus. PLoS Genet. 2012; 8(7): e1002718.
20. Mo X.B., Lu X., Zhang Y.H., Zhang Z.L., Deng F.Y., Lei S.F. Gene-based association analysis identified novel genes associated with bone mineral density. PLoS One. 2015; 10(3): e0121811.
21. Morrison N.A., Yeoman R., Kelly P.J., Eisman J.A. Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin. Proc. Natl. Acad. Sci. USA. 1992; 89(15): 6665-6669.
22. Pyott S.M., Tran T.T., Leistritz D.F., Pepin M.G., Mendelsohn N.J., Temme R.T., Fernandez B.A., Elsayed S.M., Elsobky E., Verma I., Nair S., Turner E.H., Smith J.D., Jarvik G.P., Byers P.H. WNT1 mutations in families affected by moderately severe and progressive recessive osteogenesis imperfecta. Am. J. Hum. Genet. 2013; 92(4): 590-597.
23. Rachner T.D., Khosla S., Hofbauer L.C. Osteoporosis: now and the future. Lancet. 2011; 377(9773): 1276-1287.
24. Riancho J.A., Olmos J.M., Pineda B., Garcia-Ibarbia C., Pérez-Núñez M.I., Nan D.N., Velasco J., Cano A., Garcia-Pérez M.A., Zarrabeitia M.T., Gonzalez-Macias J. Wnt receptors, bone mass, and fractures: gene-wide association analysis of LRP5 and LRP6 polymorphisms with replication. Eur. J. Endocrinol. 2011; 164(1): 123-131.
25. Rojano-Mejia D., Coral-Vazquez R.M., Espinosa L.C., Lôpez-Medina G., Aguirre-Garcia M.C., Coronel A., Canto P JAG1 and COL1A1 polymorphisms and haplotypes in relation to bone mineral density variations in postmenopausal Mexican-Mestizo Women. Age (Dordr.). 2013; 35(2): 471-478.
26. Sassi R., Sahli H., Souissi C., El Mahmoudi H., Zouari B., Ben Ammar E.l., Gaaied A., Sellami S., Ferrari S.L. Association of LRP5 genotypes with osteoporosis in Tunisian post-menopausal women. BMC Musculoskelet. Disord. 2014; 15(1): 144.
27. Sims A.M., Shephard N., Carter K., Doan T., Dowling A., Duncan E.L., Eisman J., Jones G., Nicholson G., Prince R., Seeman E., Thomas G., Wass J.A., Brown M.A. Genetic analyses in a sample of individuals with high or low BMD shows association with multiple Wnt pathway genes. J. Bone Miner. Res. 2008; 23(4): 499-506.
28. Tsang V., Fry R.C., Niculescu M.D., Rager J.E., Saunders J., Paul D.S., Zeisel S.H., Waalkes M.P, Stÿblo M., Drobna Z. The epigenetic effects of a high prenatal folate intake in male mouse fetuses exposed in utero to arsenic. Toxicol. Appl. Pharmacol. 2012; 264(3): 439-450.
29. Urano T., Inoue S. Genetics of osteoporosis. Biochem. Biophys. Res. Commun. 2014; 452(2): 287-293.
30. Wang Y., Li Y.P., Paulson C., Shao J.Z., Zhang X., Wu M., Chen W. Wnt and the Wnt signaling pathway in bone development and disease. Front. Biosci. (Landmark Ed.). 2014; 19: 379-407.
31. Wu S., Liu Y., Zhang L., Han Y., Lin Y., Deng H.W. Genome-wide approaches for identifying genetic risk factors for osteoporosis. Genome Med. 2013; 5(5): 44.
32. Yi J., Cai Y., Yao Z., Lin J. Genetic analysis of the relationship between bone mineral density and low-density lipoprotein receptor-related protein 5 gene polymorphisms. PLoS One. 2013; 8(12): e85052.
33. Zheng H.F., Tobias J.H., Duncan E., Evans D.M., Eriksson J., Paternoster L., Yerges-Armstrong L.M., Lehtimäki T., Bergström U., Kähönen M., Leo P.J., Raitakari O., Laaksonen M., Nicholson G.C., Viikari J., Ladouceur M., Lyytikäinen L.P., Medina-Gomez C., Rivadeneira F., Prince R.L., Sievanen H., Leslie W.D., Mellström D., Eisman J.A., Movérare-Skrtic S., Goltzman D., Hanley D.A., Jones G., St Pourcain B., Xiao Y., Timpson N.J., Smith G.D., Reid I.R., Ring S.M., Sambrook P.N., Karlsson M., Dennison E.M., Kemp J.P., Danoy P., Sayers A., Wilson S.G., Nethander M., McCloskey E., Vandenput L., Eastell R., Liu J., Spector T., Mitchell B.D., Streeten E.A., Brommage R., Pettersson-Kymmer U., Brown M.A., Ohlsson C., Richards J.B., Lorentzon M. WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk. PLoS Genet. 2012; 8(7): e1002745.
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For citations:
Mailyan E.A. MULTIFACTORIAL PATHOGENESIS OF OSTEOPOROSIS AND THE ROLE OF GENES OF CANONICAL WNT-SIGNALING PATHWAY. Osteoporosis and Bone Diseases. 2015;18(2):15-19. (In Russ.)
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