Skip to main content

Advertisement

Log in

The Epigenome at the Crossroad Between Social Factors, Inflammation, and Osteoporosis Risk

  • Review Paper
  • Published:
Clinical Reviews in Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Both genetic and environmental factors are involved in the pathogenesis of osteoporosis and other skeletal disorders. Epidemiological studies have revealed an influence of a variety of social factors, including socioeconomic status (SES) on the risk of osteoporosis. The mechanisms involved are complex and still incompletely elucidated. Nevertheless, a variety of clinical risk factors known to influence skeletal homeostasis have been reported as being socially patterned, including nutrition, exercise, and other lifestyles, among others. These factors may impact the skeleton through a variety of mechanisms. Among them, there is increasing evidence for a role of DNA methylation and other epigenetic mechanisms. Indeed, several studies of human cohorts and experimental models showed that social deprivation is associated with changes in the methylation pattern of a number of genes, including some involved in stress and inflammatory responses. The influence of socioeconomic factors may be important not only during postnatal life but also in utero and may be transmitted to future generations by its direct effect on peripheral and target tissues and perhaps through epigenetic inheritance. Although the exact relevance of these pathways in humans has not been fully elucidated yet, they bring attention to the influences of social factors on the skeletal health of the individuals and their descendants. Therefore, they also bring forward our responsibility for both present and future generations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Gur A, Sarac AJ, Nas K, Cevik R. The relationship between educational level and bone mineral density in postmenopausal women. BMC Fam Pract. 2004;5:18.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Amiri M, Nabipour I, Larijani B, Beigi S, Assadi M, Amiri Z, et al. The relationship of absolute poverty and bone mineral density in postmenopausal Iranian women. Int J Public Health. 2008;53:290–6.

    PubMed  Google Scholar 

  3. Crandall C, Merkin S, Seeman T, Greendale GA, Binkley N, Karlamangla AS. Socioeconomic status over the life-course and adult bone mineral density: the midlife in the U.S. study. Bone. 2012;51(1):107–13.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Goodfellow LR, Earl S, Cooper C, Harvey NC. Maternal diet, behaviour and offspring skeletal health. Int J Environ Res Public Health. 2010;53:290–6.

    Google Scholar 

  5. Harvey N, Dennison E, Cooper C. Osteoporosis: a lifecourse approach. J Bone Miner Res. 2014a;29(9):1917–25.

    Article  PubMed  Google Scholar 

  6. Barker DJP. The origins of the developmental origins theory. J Intern Med. 2007;261:412–7.

    Article  CAS  PubMed  Google Scholar 

  7. Beauchamp A, Buchbinder R, Dodson S, Batterham RW, Elsworth GR, Mcphee C, et al. Distribution of health literacy strengths and weaknesses across socio-demographic groups: a cross-sectional survey using the Health Literacy Questionnaire (HLQ). BMC Public Health. 2015;15:678.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hosking S, Buchbinder R, Pasco J, Williams L, Brennan-Olsen S. The role of health literacy in the treatment of osteoporosis. J Bone Miner Res. 2016;31:1909.

    Article  CAS  PubMed  Google Scholar 

  9. Vestergaard P, Rejnmark L, Mosekilde L. Socioeconomic aspects of fractures within universal public healthcare: a nationwide case-control study from Denmark. Scand J Public Health. 2006;34:371–7.

    Article  PubMed  Google Scholar 

  10. Brennan-Olsen SL, Page RS, Berk M, Riancho JA, Leslie WD, Wilson SG, et al. DNA methylation and the social gradient of osteoporotic fracture: a conceptual model. Bone. 2016;84:204–12.

    Article  CAS  PubMed  Google Scholar 

  11. Brennan SL, Holloway KL, Williams LJ, Kotowicz MA, Bucki-Smith G, Moloney DJ, et al. The social gradient of fractures at any skeletal site in men and women: data from the Geelong Osteoporosis Study Fracture Grid. Osteoporos Int. 2015;26(4):1351–9.

    Article  CAS  PubMed  Google Scholar 

  12. Araki Y, Mimura T. The histone modification code in the pathogenesis of autoimmune diseases. Mediat Inflamm. 2017;2017:1–12.

    Article  Google Scholar 

  13. Zhang T, Cooper S, Brockdorff N. The interplay of histone modifications—writers that read. EMBO Rep. 2015;16(11):1467–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Turinetto V, Giachino C. Histone variants as emerging regulators of embryonic stem cell identity. Epigenetics. 2015;10(7):563–73.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Schmitz SU, Grote P, Herrmann BG. Mechanisms of long noncoding RNA function in development and disease. Cell Mol Life Sci. 2016;73(13):2491–509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hassan MQ, Tye CE, Stein GS, Lian JB. Non-coding RNAs: epigenetic regulators of bone development and homeostasis. Bone. 2015;81:746–56.

    Article  CAS  PubMed  Google Scholar 

  17. Huh I, Zeng J, Park T, Yi SV. DNA methylation and transcriptional noise. Epigenetics Chromatin. 2013;6(1):9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Calvanese V, Lara E, Kahn A, Fraga MF. The role of epigenetics in aging and age-related diseases. Ageing Res Rev. 2009;8(4):268–76.

    Article  CAS  PubMed  Google Scholar 

  19. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Revews Genet. 2012;13(7):484–92.

    Article  CAS  Google Scholar 

  20. Deaton AM, Webb S, Kerr AR, Illingworth RS, Guy J, Andrews R, et al. Cell type-specific DNA methylation at intragenic CpG islands in the immune system. Genome Res. 2011;21(7):1074–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Reddington JP, Pennings S, Meehan RR. Non-canonical functions of the DNA methylome in gene regulation. Biochem J. 2013;451(1):13–23.

    Article  CAS  PubMed  Google Scholar 

  22. Ziller MJ, Gu H, Muller F, Donaghey J, Tsai LT, Kohlbacher O, et al. Charting a dynamic DNA methylation landscape of the human genome. Nature. 2013;500:477–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chiarella J, Tremblay RE, Szyf M, Provencal N, Booij L. Impact of early environment on children’s mental health: lessons from DNA methylation studies with monozygotic twins. Twin Res Hum Genet. 2015;18(6):1–12.

    Article  Google Scholar 

  24. van Dongen J, Nivard MG, Willemsen G, Hottenga J-J, Helmer Q, Dolan CV, et al. Genetic and environmental influences interact with age and sex in shaping the human methylome. Nat Commun. 2016;7:11115.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Vaiserman A. Epidemiologic evidence for association between adverse environmental exposures in early life and epigenetic variation: a potential link to disease susceptibility? Clin Epigenetics. 2015a;7(1):96.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Vaiserman AM. Epigenetic programming by early-life stress: evidence from human populations. Dev Dyn. 2015b;244(3):254–65.

    Article  CAS  PubMed  Google Scholar 

  27. Demetriou CA, van Veldhoven K, Relton C, Stringhini S, Kyriacou K, Vineis P. Biological embedding of early-life exposures and disease risk in humans: a role for DNA methylation. Eur J Clin Investig. 2015;45(3):303–32.

    Article  CAS  Google Scholar 

  28. Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A. 2008;105(44):17046–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tobi EW, Goeman JJ, Monajemi R, Gu H, Putter H, Zhang Y, et al. DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat Commun. 2014;5:5592.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Finer S, Iqbal MS, Lowe R, Ogunkolade BW, Pervin S, Mathews C, et al. Is famine exposure during developmental life in rural Bangladesh associated with a metabolic and epigenetic signature in young adulthood? A historical cohort study. BMJ Open. 2016;6(11):e011768.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tobi EW, Slieker RC, Stein AD, Suchiman HED, Eline Slagboom P, Van Zwet EW, et al. Early gestation as the critical time-window for changes in the prenatal environment to affect the adult human blood methylome. Int J Epidemiol. 2015;44(4):1211–23.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Weaver ICG, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, et al. Epigenetic programming by maternal behavior. Nat Neurosci. 2004;7(8):847–54.

    Article  CAS  PubMed  Google Scholar 

  33. Tung J, Barreiro LB, Johnson ZP, Hansen KD, Michopoulos V, Toufexis D, et al. Social environment is associated with gene regulatory variation in the rhesus macaque immune system. Proc Natl Acad Sci U S A. 2012;109(17):6490–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. McGowan PO, Sasaki A, D’Alessio AC, Dymov S, Labonté B, Szyf M, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009;12(3):342–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Provencal N, Booij L, Tremblay RE. The developmental origins of chronic physical aggression: biological pathways triggered by early life adversity. J Exp Biol. 2015;218(Pt 1):123–33.

    Article  PubMed  Google Scholar 

  36. Mcguinness D, Mcglynn LM, Johnson PCD, Macintyre A, Batty GD, Burns H, et al. Socio-economic status is associated with epigenetic differences in the pSoBid cohort. Int J Epidemiol. 2012;41(1):151–60.

    Article  PubMed  Google Scholar 

  37. Stringhini S, Polidoro S, Sacerdote C, Kelly RS, Van Veldhoven K, Agnoli C, et al. Life-course socioeconomic status and DNA methylation of genes regulating inflammation. Int J Epidemiol. 2015;44(4):1320–30.

    Article  PubMed  Google Scholar 

  38. Needham BL, Smith JA, Zhao W, Wang X, Kardia SLR, Shively CA, et al. Life course socioeconomic status and DNA methylation in genes related to stress reactivity and inflammation: the multi-ethnic study of atherosclerosis. Epigenetics. 2015;10:958–69.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kim D, Kubzansky LD, Baccarelli A, Sparrow D, Spiro A, Tarantini L, et al. Psychological factors and DNA methylation of genes related to immune/inflammatory system markers: the VA Normative Aging Study. BMJ Open. 2016;6(1):e009790.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Bam M, Yang X, Zumbrun EE, Zhong Y, Zhou J, Ginsberg JP, et al. Dysregulated immune system networks in war veterans with PTSD is an outcome of altered miRNA expression and DNA methylation. Sci Rep. 2016;6:31209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bollati V, Favero C, Albetti B, Tarantini L, Moroni A, Byun HM, et al. Nutrients intake is associated with DNA methylation of candidate inflammatory genes in a population of obese subjects. Nutrients. 2014;6(10):4625–39.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kok DE, Dhonukshe-Rutten RA, Lute C, Heil SG, Uitterlinden AG, van der Velde N, et al. The effects of long-term daily folic acid and vitamin B12 supplementation on genome-wide DNA methylation in elderly subjects. Clin Epigenetics. 2015;7:121.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lenkov K, Lee MH, Lenkov OD, Swafford A, Fernald RD. Epigenetic DNA methylation linked to social dominance. PLoS One. 2015;10(12):1–11.

    Article  Google Scholar 

  44. Hoffmann A, Spengler D. DNA memories of early social life. Neuroscience. 2014;264:64–75.

    Article  CAS  PubMed  Google Scholar 

  45. Swartz JR, Hariri AR, Williamson DE. An epigenetic mechanism links socioeconomic status to changes in depression-related brain function in high-risk adolescents. Mol Psychiatry. 2017;22:209–14.

    Article  CAS  PubMed  Google Scholar 

  46. Ligthart S, Marzi C, Aslibekyan S, Mendelson MM, Conneely KN, Tanaka T, et al. DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases. Genome Biol. 2016;17(1):255.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Kreuz S, Fischle W. Oxidative stress signaling to chromatin in health and disease. Epigenomics. 2016;8(6):843–62.

    Article  CAS  PubMed  Google Scholar 

  48. Planello AC, Singhania R, Kron KJ, Bailey SD, Roulois D, Lupien M, et al. Pre-neoplastic epigenetic disruption of transcriptional enhancers in chronic inflammation. Oncotarget. 2015;7(13):1–15.

    Google Scholar 

  49. Stánitz É, Juhász K, Gombos K, Gőcze K, Tóth C, Kiss I. Alteration of miRNA expression correlates with lifestyle, social and environmental determinants in esophageal carcinoma. Anticancer Res. 2015;35:1091–7.

    PubMed  Google Scholar 

  50. Delgado-Calle J, Riancho JA. The role of DNA methylation in common skeletal disorders. Biology (Basel). [Internet]2012;1:698–713.

    CAS  Google Scholar 

  51. Delgado-Calle J, Garmilla P, Riancho JA. Do epigenetic marks govern bone mass and homeostasis? Curr Genomics. 2012a;13(3):252–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Delgado-Calle J, Sanudo C, Bolado A, Fernandez AF, Arozamena J, Pascual-Carra MA, et al. DNA methylation contributes to the regulation of sclerostin expression in human osteocytes. J Bone Miner Res. 2012b;27:926–37.

    Article  CAS  PubMed  Google Scholar 

  53. Lian JB, Stein GS, van Wijnen AJ, Stein JL, Hassan MQ, Gaur T, et al. MicroRNA control of bone formation and homeostasis. Nat Rev Endocrinol. 2012;8(4):212–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Jintaridth P, Tungtrongchitr R, Preutthipan S, Mutirangura A. Hypomethylation of Alu elements in post-menopausal women with osteoporosis. PLoS One. 2013;8(8):e70386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Delgado-Calle J, Fernandez AF, Sainz J, Zarrabeitia MT, Sanudo C, Garcia-Renedo R, et al. Genome-wide profiling of bone reveals differentially methylated regions in osteoporosis and osteoarthritis. Arthritis Rheum. 2013;65:197–205.

    Article  CAS  PubMed  Google Scholar 

  56. 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;94:414–22.

    Article  CAS  PubMed  Google Scholar 

  57. Riancho JA, Salas E, Zarrabeitia MT, Olmos JM, Amado JA, Fernandez-Luna JL, et al. Expression and functional role of nitric oxide synthase inhibitors in osteoblast-like cells. J Bone Miner Res. 1995;10:439–46.

    Article  CAS  PubMed  Google Scholar 

  58. Harvey NC, Lillycrop KA, Garratt E, Sheppard A, McLean C, Burdge G, et al. Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content. Calcif Tissue Int. 2012;90:120–7.

    Article  CAS  PubMed  Google Scholar 

  59. Harvey NC, Sheppard A, Godfrey KM, McLean C, Garratt E, Ntani G, et al. Childhood bone mineral content is associated with methylation status of the RXRA promoter at birth. J Bone Miner Res. 2014b;29(3):600–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Papaioannou G. MiRNAs in bone development. Curr Genomics. 2015;16(6):427–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Seeliger C, Er B, van Griensven M. miRNAs related to skeletal diseases. Stem Cells Dev. 2016;25:1261–8.

    Article  CAS  PubMed  Google Scholar 

  62. Herman JP, Mcklveen JM, Ghosal S, Kopp B, Wulsin A, Makinson R, et al. Regulation of the hypothalamic-pituitary-adrenocortical stress response. Compr Physiol. 2016;6(2):603–21.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Gold PW. The organization of the stress system and its dysregulation in depressive illness. Mol Psychiatry. 2015;20(1):32–47.

    Article  CAS  PubMed  Google Scholar 

  64. Waltes R, Chiocchetti AG, Freitag CM. The neurobiological basis of human aggression: a review on genetic and epigenetic mechanisms. Am J Med Genet Part B Neuropsychiatr Genet. 2016;171(5):650–75.

    Article  Google Scholar 

  65. Hunter AL, Minnis H, Wilson P. Altered stress responses in children exposed to early adversity: a systematic review of salivary cortisol studies. Stress. 2011;14(6):614–26.

    Article  CAS  PubMed  Google Scholar 

  66. Napal J, Amado JA, Riancho JA, Olmos JA, Gonzalez-Macias J. Stress decreases the serum level of osteocalcin. Bone Miner. 1993;21:113–8.

    Article  CAS  PubMed  Google Scholar 

  67. Hartmann K, Koenen M, Schauer S, Wittig-Blaich S, Ahmad M, Baschant U, et al. Molecular actions of glucocorticoids in cartilage and bone during health, disease, and steroid therapy. Physiol Rev. 2016;96(2):409–47.

    Article  CAS  PubMed  Google Scholar 

  68. Lorenzo J, Horowitz M, Choi Y. Osteoimmunology: interactions of the bone and immune system. Endocr Rev. 2008;29(4):403–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Schett G, Dayer J-M, Manger B. Interleukin-1 function and role in rheumatic disease. Nat Rev Rheumatol. 2015;12(1):14–24.

    Article  PubMed  Google Scholar 

  70. Zupan J, Jeras M, Marc J. Osteoimmunology and the influence of pro-inflammatory cytokines on osteoclasts. Biochem Medica. 2013;23(1):43–63.

    Article  CAS  Google Scholar 

  71. Pietschmann P, Mechtcheriakova D, Meshcheryakova A, Föger-Samwald U, Ellinger I. Immunology of osteoporosis: a mini-review. Gerontology. 2016;62(2):128–37.

    Article  CAS  PubMed  Google Scholar 

  72. Bygren LO, Tinghög P, Carstensen J, Edvinsson S, Kaati G, Pembrey ME, et al. Change in paternal grandmothers’ early food supply influenced cardiovascular mortality of the female grandchildren. BMC Genet. 2014;15(1):12.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to José A. Riancho.

Ethics declarations

Funding

JAR is funded by Instituto de Salud Carlos III (PI12/615, PI16/915, that can be co-funded by EU FEDER funds). SLB-O is funded by a National Health and Medical Research Council (NHMRC) of Australia Career Development Fellowship (1107510).

Conflict of Interest

The authors declare that they have no conflict of interest.

Research Involving Human Participants and/or Animals

The article does not contain any studies with human or animal subjects performed by the any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Riancho, J.A., Brennan-Olsen, S.L. The Epigenome at the Crossroad Between Social Factors, Inflammation, and Osteoporosis Risk. Clinic Rev Bone Miner Metab 15, 59–68 (2017). https://doi.org/10.1007/s12018-017-9229-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12018-017-9229-5

Keywords

Navigation