Advertisement

Osteoporosis International

, Volume 25, Issue 2, pp 783–786 | Cite as

IL-17A-mediated sRANK ligand elevation involved in postmenopausal osteoporosis

  • I. Molnár
  • I. Bohaty
  • É. Somogyiné-Vári
Short Communication

Abstract

Summary

The role of proinflammatory IL-17 cytokine was studied in postmenopausal bone loss between 31 osteopenic and 41 osteoporotic women. The effect of serum IL-17A, soluble receptor activator of NF-κB (sRANK) ligand, and osteoprotegerin (OPG) levels on lumbar bone mineral densities was measured. The results demonstrated an increased IL-17A-mediated sRANK ligand elevation in postmenopausal osteoporotic bone loss.

Introduction

IL-17 proinflammatory cytokine is a new inducer of bone loss. Postmenopausal osteoporosis represents a cross talk between estrogen deprivation and increased immune reactivity. The role of IL-17 was studied in the bone loss of postmenopausal osteoporosis.

Methods

Serum IL-17A, sRANK ligand, and OPG levels were investigated on bone mineral densities (BMDs) in the total lumbar (L1–L4) region in 18 pre- and 72 postmenopausal women. IL-17A, sRANK ligand, OPG levels, and BMDs were measured with enzyme-linked immunosorbent assay (ELISA) and dual-energy X-ray absorptiometry (DXA).

Results

Increased serum IL-17A, sRANK ligand, and OPG levels were demonstrated in postmenopausal osteoporotic women compared to osteopenic women (3.65 ± 0.61 vs 3.31 ± 0.43 ng/ml for IL-17A, P < 0.007; 2.88 ± 0.84 vs 2.49 ± 0.61 ng/ml for sRANK ligand, P < 0.027; and 1.43 ± 0.07 vs 1.39 ± 0.07 ng/ml for OPG, P < 0.038). In postmenopausal women, IL-17A levels correlated inversely with total lumbar BMDs (P < 0.008, r = −0.279) and positively with sRANK ligand levels (P < 0.0001, r = 0.387) or the ratio of sRANK ligand and OPG (P < 0.013, r = 0.261), but did not with OPG levels alone.

Conclusion

Increased IL-17A levels are involved in postmenopausal osteoporosis, playing a role in the bone-resorpting processes.

Keywords

Bone mineral density Interleukin-17 Osteoporosis Postmenopause sRANK ligand 

Notes

Conflicts of interest

None.

References

  1. 1.
    Horowitz MC (1993) Cytokines and estrogen in bone: anti-osteoporotic effects. Science 260:626–627PubMedCrossRefGoogle Scholar
  2. 2.
    Riggs BL (2000) The mechanisms of estrogen regulation of bone resorption. J Clin Invest 106:1203–1204PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Stolina M, Schett G, Dwyer D, Vonderfecht S, Middleton S, Duryea D, Pachrco E, Van G, Bolon B, Feige U, Zack D, Kostenuik P (2009) RANKL inhibition by osteoprotegerin prevents bone loss without affecting local or systemic inflammation parameters in two rat arthritis models: comparison anti-TNFα or anti-IL-1 therapies. Arthritis & Therapy. doi: 10.1186/ ar2879 Google Scholar
  4. 4.
    Udagawa N, Kotake S, Kamatani N, Takahashi N, Suda T (2002) The molecular mechanism of osteoclastogenesis in rheumatoid arthritis. Arthritis Res 4:281–289PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Miossec P, Korm T, Kuchroo VK (2009) Interleukin17 and type 17 helper T cells. N Engl J Med 361:888–898PubMedCrossRefGoogle Scholar
  6. 6.
    Pène J, Chevalier S, Preisser L, Vénéreau E, Guilleux MH, Ghannam S, Molès JP, Danger Y, Ravon E, Lesaux S, Yssel H, Gascan H (2008) Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J Immunol 180:7423–7430PubMedGoogle Scholar
  7. 7.
    Kotake S, Udagawa N, Hakoda M, Mogi M, Yano K, Tsuda E, Takahashi K, Furuya T, Ishiyama S, Kim HJ, Saito S, Nishikawa T, Takahashi N, Togari A, TomatsuT ST, Kamatani N (2001) Activated human T cells directly induce osteoclastogenesis from human monocytes. Arthritis & Rheumatism 44:1003–1012CrossRefGoogle Scholar
  8. 8.
    Chabaud M, Lubberts E, Joosten L, van den Berg W, Miossec P (2001) IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis. Arthritis Res 3:168–177PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Geusens P, Lems WF (2011) Osteoimmunology and osteoporosis. Arthritis Res 13:242–257CrossRefGoogle Scholar
  10. 10.
    Gaffen SL (2004) Biology of recently discovered cytokines: interleukin-17—a unique inflammatory cytokine with roles in bone biology and arthritis. Arthritis Res Ther 6:240–247PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, Tanaka S, Kodama T, Akira S, Iwakura Y, Cua DJ, Takayanagi H (2006) Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 203:2673–2682PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Ley K, Smith E, Stark MA (2006) IL-17A-producing neutrophil-regulatory Tn lymphocytes. Immunol Res 34:229–242PubMedCrossRefGoogle Scholar
  13. 13.
    Braun T, Zwerina J (2011) Positive regulators of osteoclastogenesis and bone resorption in rheumatoid arthritis. Arthritis Res Ther 13:235PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Das S, Crockett JC (2013) Osteoporosis—a current view of pharmacological prevention and treatment. Drug Des Devel Ther 7:435–448PubMedCentralPubMedGoogle Scholar
  15. 15.
    Teitelbaum SL (2004) Postmenopausal osteoporosis, T cells, and immune dysfunction. PNAS 101:16711–16712PubMedCrossRefGoogle Scholar
  16. 16.
    Tyagi AM, Srivastava K, Mansoori MN, Trivedi R, Chattopadhyay N, Singh D (2012) Estrogen deficiency induces the differentiation of IL-17 secreting Th17 cells: a new candidate in the pathogenesis of osteoporosis. Plos One 7:e44552–e44564PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Molnár I, Bohaty I, Somogyiné-Vári É (2014) A high prevalence of increased IL-17A serum levels in postmenopausal estrogen deficiency. Menopause. doi: 10.1097/GME.0000000000000125

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2013

Authors and Affiliations

  1. 1.Immunoendocrinology and Osteoporosis CentreEndoMedDebrecenHungary
  2. 2.Regional Centre of Hungarian National Blood Transfusion ServiceDebrecenHungary

Personalised recommendations