Advertisement

Clinical Rheumatology

, Volume 38, Issue 4, pp 989–995 | Cite as

Sclerostin rather than Dickkopf-1 is associated with mSASSS but not with disease activity score in patients with ankylosing spondylitis

  • Wenjia Sun
  • Lizhen Tian
  • Lichun Jiang
  • Songzhao Zhang
  • Meiju Zhou
  • Jianing Zhu
  • Jing XueEmail author
Original Article

Abstract

Objective

To determine the serum levels of Dickkopf-1 (DKK-1) and sclerostin, as well as their correlations with the structural damage assessed by modified stoke ankylosing spondylitis spine score (mSASSS) and the disease activity evaluated by ankylosing spondylitis disease activity score (ASDAS) in patients with ankylosing spondylitis (AS).

Methods

Eighty-eight AS patients, 26 rheumatoid arthritis (RA) patients, and 26 age- and gender-matched healthy controls (HC) were collected from rheumatic clinic of the Second Affiliated Hospital of Zhejiang University, School of Medicine, between March 2015 and July 2015. Demographic data, parameters of ASDAS, and image evaluations of spine (i.e., mSASSS) were collected. The serum levels of DKK-1 and sclerostin were measured using commercially available ELISA kits.

Results

Both DKK-1 and sclerostin were significantly higher in the AS patients than in the controls (1855 ± 84.58 vs. 1406 ± 99.76 pg/ml and 106 ± 6.75 vs. 62.78 ± 6.39 pmol/l, respectively, P < 0.05). The correlation analysis suggested a negative correlation between serum sclerostin and mSASSS (P = 0.019, r2 = 0.062). DKK-1 had a trend of positive correlation with mSASSS, but was not statistically significant (P > 0.05). There was no association between the serum levels of DKK-1 or sclerostin and disease activity assessed by ASDAS (P > 0.05). DKK-1 and sclerostin had a negative correlation (P = 0.013, r2 = 0.07).

Conclusion

In the present study, the expressions of serum DKK-1 and sclerostin were independent of disease activity. Sclerostin was negatively correlated with the mSASSS, which suggests that sclerostin may be a potential marker indicating the spine ossification process in AS. The specific mechanism remains to be investigated.

Keywords

Ankylosing spondylitis AS disease activity score (ASDAS) Dickkopf-1 (DKK-1) Modified stoke ankylosing spondylitis spine score (mSASSS) Sclerostin 

Notes

Funding information

The study was sponsored by fund from the Jinhua city Science and Technology Bureau (2015-3-040).

Compliance with ethical standards

The study was performed according to the Declaration of Helsinki, and approved by the ethics committee of the Second Affiliated Hospital of Zhejiang University, School of Medicine.

Disclosures

None.

References

  1. 1.
    Braun J, Sieper J (2007) Ankylosing spondylitis. Lancet 369:1379–1390CrossRefGoogle Scholar
  2. 2.
    Sieper J, Poddubnyy D (2017) Axial spondyloarthritis. Lancet 390:73–84CrossRefGoogle Scholar
  3. 3.
    Smith JA (2015) Update on ankylosing spondylitis: current concepts in pathogenesis. Curr Allergy Asthma Rep 15:489CrossRefGoogle Scholar
  4. 4.
    Zhou Y, Wang T, Hamilton JT, Chen D (2017) Wnt/β-catenin signaling in osteoarthritis and in other forms of arthritis. Curr Rheumatol Rep 19:53CrossRefGoogle Scholar
  5. 5.
    Tsui FW, Tsui HW, Las Heras F, Pritzker KP, Inman RD (2014) Serum levels of novel noggin and sclerostin-immune complexes are elevated in ankylosing spondylitis. Ann Rheum Dis 73:1873–1879CrossRefGoogle Scholar
  6. 6.
    Corr M (2014) Wnt signaling in ankylosing spondylitis. Clin Rheumatol 33:759–762CrossRefGoogle Scholar
  7. 7.
    MacDonald BT, Tamai K, He X (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17:9–26CrossRefGoogle Scholar
  8. 8.
    Xie W, Zhou L, Li S, Hui T, Chen D (2016) Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis. Ann N Y Acad Sci 1364:25–31CrossRefGoogle Scholar
  9. 9.
    Klavdianou K, Liossis SN, Sakkas L, Daoussis D (2017) The role of Dickkopf-1 in joint remodeling and fibrosis: a link connecting spondyloarthropathies and scleroderma? Semin Arthritis Rheum 46:430–438CrossRefGoogle Scholar
  10. 10.
    Wu M, Chen M, Ma Y, Yang J, Han R, Yuan Y, Hu X, Wang M, Zhang X, Xu S, Liu R, Jiang G, Xu J, Shuai Z, Zou Y, Pan G, Pan F (2018) Dickkopf-1 in ankylosing spondylitis: review and meta-analysis. Clin Chim Acta 481:177–183CrossRefGoogle Scholar
  11. 11.
    Daoussis D, Andonopoulos AP, Liossis SN (2010) Wnt pathway and IL-17: novel regulators of joint remodeling in rheumatic diseases. Looking beyond the RANK-RANKL-OPG axis. Semin Arthritis Rheum 39:369–383CrossRefGoogle Scholar
  12. 12.
    Zhang L, Ouyang H, Xie Z, Liang ZH, Wu XW (2016) Serum DKK-1 level in the development of ankylosing spondylitis and rheumatic arthritis: a meta-analysis. Exp Mol Med 48:e228CrossRefGoogle Scholar
  13. 13.
    Niu CC, Lin SS, Yuan LJ, Chen LH, Yang CY, Chung AN, Lu ML, Tsai TT, Lai PL, Chen WJ (2017) Correlation of blood bone turnover biomarkers and Wnt signaling antagonists with AS, DISH, OPLL, and OYL. BMC Musculoskelet Disord 18:61CrossRefGoogle Scholar
  14. 14.
    Wanders AJ, Landewé RB, Spoorenberg A, Dougados M, van der Linden S, Mielants H et al (2004) What is the most appropriate radiologic scoring method for ankylosing ? Arthritis Rheum 50:2622–2632CrossRefGoogle Scholar
  15. 15.
    Chou CT (2013) How to translate basic knowledge into clinical application of biologic therapy in spondyloarthritis. Clin Dev Immunol 2013:369202CrossRefGoogle Scholar
  16. 16.
    Liang H, Li WR, Zhang H, Tian X, Wei W, Wang CM (2015) Concurrent intervention with exercises and stabilized tumor necrosis factor inhibitor therapy reduced the disease activity in patients with ankylosing spondylitis. Medicine (Baltimore) 94:e2254CrossRefGoogle Scholar
  17. 17.
    Osman MS, Maksymowych WP (2017) An update on the use of tumor necrosis factor alpha inhibitors in the treatment of ankylosing spondylitis. Expert Rev Clin Immunol 13:125–131CrossRefGoogle Scholar
  18. 18.
    Uderhardt S, Diarra D, Katzenbeisser J, David JP, Zwerina J, Richards W, Kronke G, Schett G (2010) Blockade of Dickkopf (DKK)-1 induces fusion of sacroiliac joints. Ann Rheum Dis 69:592–597CrossRefGoogle Scholar
  19. 19.
    Heiland GR, Appel H, Poddubnyy D, Zwerina J, Hueber A, Haibel H, Baraliakos X, Listing J, Rudwaleit M, Schett G, Sieper J (2012) High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis. Ann Rheum Dis 71:572–574CrossRefGoogle Scholar
  20. 20.
    Sakellariou GT, Iliopoulos A, Konsta M, Kenanidis E, Potoupnis M, Tsiridis E, Gavana E, Sayegh FE (2017) Serum levels of DKK-1, sclerostin and VEGF in patients with ankylosing spondylitis and their association with smoking, and clinical, inflammatory and radiographic parameters. Jt Bone Spine 84:309–315CrossRefGoogle Scholar
  21. 21.
    Daoussis D, Liossis SN, Solomou EE, Tsanaktsi A, Bounia K, Karampetsou MEE et al (2010) Evidence that DKK-1 is dysfunctional in ankylosing spondylitis. Arthritis Rheum 62:150–158CrossRefGoogle Scholar
  22. 22.
    Korkosz M, Gąsowski J, Leszczyński P, Pawlak-Buś K, Jeka S, Kucharska E, Grodzicki T (2013) High disease activity in ankylosing spondylitis is associated with increased serum sclerostin level and decreased wingless protein-3a signaling but is not linked with greater structural damage. BMC Musculoskelet Disord 14:99–104CrossRefGoogle Scholar
  23. 23.
    Ustun N, Tok F, Kalyoncu U, Motor S, Yuksel R, Yagiz AE, Guler H, Turhanoglu AD (2014) Sclerostin and Dkk-1 in patients with ankylosing spondylitis. Acta Reumatol Port 39:146–151Google Scholar
  24. 24.
    Kwon SR, Lim MJ, Suh CH, Park SG, Hong YS, Yoon BY, Kim HA, Choi HJ, Park W (2012) Dickkopf-1 level is lower in patients with ankylosing spondylitis than in healthy people and is not influenced by anti-tumor necrosis factor therapy. Rheumatol Int 32:2523–2527CrossRefGoogle Scholar
  25. 25.
    Klavdianou K, Liossis SN, Papachristou DJ, Theocharis G, Sirinian C, Kottorou A, Filippopoulou A, Andonopoulos AP, Daoussis D (2016) Decreased serotonin levels and serotonin-mediated osteoblastic inhibitory signaling in patients with ankylosing spondylitis. J Bone Miner Res 31:630–639CrossRefGoogle Scholar
  26. 26.
    Ke HZ, Richards WG, Li X, Ominsky MS (2012) Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev 33:747–783CrossRefGoogle Scholar
  27. 27.
    Yucong Z, Lu L, Shengfa L, Yongliang Y, Ruguo S, Yikai L (2014) Serum functional dickkopf-1 levels are inversely correlated with radiographic severity of ankylosing spondylitis. Clin Lab 60:1527–1531CrossRefGoogle Scholar
  28. 28.
    Costa AG, Cremers S, Bilezikian JP (2017) Sclerostin measurement in human disease: validity and current limitations. Bone 96:24–28CrossRefGoogle Scholar
  29. 29.
    Sellas I, Fernandez A, Juanola Roura X, Alonso Ruiz A, Rosas J, Medina Luezas J, Collantes Estevez E et al (2017) Clinical utility of the ASDAS index in comparison with BASDAI in patients with ankylosing spondylitis (Axis Study). Rheumatol Int 37:1817–1823CrossRefGoogle Scholar
  30. 30.
    Machado PM, Landewé R, Heijde DV, Assessment of SpondyloArthritis international Society (ASAS) (2018) Ankylosing Spondylitis Disease Activity Score (ASDAS): 2018 update of the nomenclature for disease activity states. Ann Rheum Dis 77:1539–1540Google Scholar
  31. 31.
    Rossini M, Viapiana O, Idolazzi L, Ghellere F, Fracassi E, Troplini S, Povino MR, Kunnathully V, Adami S, Gatti D (2016) Higher level of Dickkopf-1 is associated with low bone mineral density and higher prevalence of vertebral fractures in patients with ankylosing spondylitis. Calcif Tissue Int 98:438–445CrossRefGoogle Scholar
  32. 32.
    Muntean L, Lungu A, Gheorghe SR, Valeanu M, Craciun AM, Felea I et al (2016) Elevated serum levels of Sclerostin are associated with high disease activity and functional impairment in patients with axial spondyloarthritis. Clin Lab 62:589–597CrossRefGoogle Scholar
  33. 33.
    Appel H, Ruiz-Heiland G, Listing J, Zwerina J, Herrmann M, Mueller R, Haibel H, Baraliakos X, Hempfing A, Rudwaleit M, Sieper J, Schett G (2009) Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum 60:3257–3262CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  • Wenjia Sun
    • 1
  • Lizhen Tian
    • 1
    • 2
  • Lichun Jiang
    • 1
    • 3
  • Songzhao Zhang
    • 4
  • Meiju Zhou
    • 1
  • Jianing Zhu
    • 1
  • Jing Xue
    • 1
    Email author
  1. 1.Department of Rheumatology, School of MedicineThe Second Affiliated Hospital of Zhejiang UniversityHangzhouChina
  2. 2.Department of RheumatologyJinhua Hospital of Traditional Chinese MedicineJinhuaChina
  3. 3.Department of RheumatologyThe First Hospital of JiaxingJiaxingChina
  4. 4.Department of Clinical LaboratoryThe Second Affiliated Hospital of Zhejiang University, School of MedicineHangzhouChina

Personalised recommendations