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Association of serum Dkk-1 levels with β-catenin in patients with postmenopausal osteoporosis

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Summary

Wnt signaling plays an important role in the bone development and remodeling. The Wnt antagonist Dkk-1 is a potent inhibitor of bone formation. The aims of this study were firstly to compare the serum Dkk-1 levels in postmenopausal osteoporosis patients with age-matched healthy controls, and secondly, to assess the possible relationship between Dkk-1 and β-catenin, sclerostin, or bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] in the setting of postmenopausal osteoporosis. A total of 350 patients with postmenopausal osteoporosis and 150 age-matched healthy controls were enrolled, and the serum levels of Dkk-1, β-catenin, sclerostin, OPG, and RANKL were detected by ELISA, and bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] were measured by Roche electrochemiluminescence system in two groups. Serum Dkk-1 levels were significantly higher in postmenopausal osteoporosis group than in control group (P<0.001). Univariate analyses revealed that serum Dkk-1 levels were weakly negatively correlated to β-catenin (r=−0.161, P=0.003) and OPG (r=−0.106, P=0.047), while multiple regression analysis showed a negative correlation between serum Dkk-1 levels with β-catenin (β=−0.165, P=0.009) and BMD (β=−0.139, P=0.027), and a positive correlation between serum Dkk-1 levels and CTX (β=0.122, P=0.040) in postmenopausal osteoporosis group. No similar correlations ware observed in control group. The results provided evidence for the role of Dkk-1 in bone metabolism and demonstrated the link of Dkk-1 and Wnt/β-catenin in some ways.

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References

  1. Sambrook P, Cooper C. Osteoporosis. Lancet, 2006,367:2010–2018

    Article  CAS  PubMed  Google Scholar 

  2. Gifre L, Ruiz-Gaspà S, Monegal A, et al. Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. Bone, 2013,57(1):272–276

    Article  CAS  PubMed  Google Scholar 

  3. Chamorro MN, Schwartz DR, Vonica A, et al. FGF-20 and DKK1 are transcriptional targets of beta-catenin and FGF-20 is implicated in cancer and development. EMBO J, 2005,24(1):73–84

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Voorzaner-Rousselot N, Goehrig D, Facon T, et al. Platelet is a major contributor to circulating levels of Dickkopf-1: clinical implications in patients with multiple myeloma. Bri J Haematol, 2009,145(2):264–266

    Article  Google Scholar 

  5. Pinzone JJ, Hall BM, Thudi NK, et al. The role of Dickkopf-1 in bone development, homeostasis, and disease. Blood, 2009,113(3):517–525

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Morvan F, Boulukos K, Clément-Lacroix P, et al. Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Mineral Res, 2006,21(6):934–945

    Article  CAS  Google Scholar 

  7. Li J, Sarosi I, Cattley RC, et al. Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone, 2006,39(4):754–766

    Article  CAS  PubMed  Google Scholar 

  8. Wang FS, Ko JY, Yeh DW, et al. Modulation of dickkopf-1 attenuates glucocorticoid induction of osteoblast apoptosis, adipocytic differentiation, and bone mass loss. Endocrinology, 2008,149(4):1793–1801

    Article  CAS  PubMed  Google Scholar 

  9. Wang FS, Ko JY, Lin CL, et al. Knocking down dickkopf-1 alleviates estrogen deficiency induction of bone loss. A histomorphological study in ovariectomized rats. Bone, 2007,40(2):485–492

    Article  CAS  PubMed  Google Scholar 

  10. Terpos E, Dimopoulos MA, Sezer O. The effect of novel anti-myeloma agents on bone metabolism of patients with multiple myeloma. Leukemia, 2007,21(9):1875–1884

    Article  CAS  PubMed  Google Scholar 

  11. Krishnan V, Bryant HU, Macdougald OA. Regulation of bone mass by Wnt signaling. J Clin Inv, 2006,116(5):1202–1209

    Article  CAS  Google Scholar 

  12. Rawadi G, Vayssière B, Dunn F, et al. BMP-2 controls alkaline phosphatase expression and osteoblast mineralization by a Wnt autocrine loop. J Bone Mineral Res, 2003,18(10):1842–1853

    Article  CAS  Google Scholar 

  13. Suzuki A, Ozono K, Kubota T, et al. PTH/cAMP/PKA signaling facilitates canonical Wnt signaling via inactivation of glycogen synthase kinase-3beta in osteoblastic Saos-2 cells. J Cell Biochem, 2008,104(1):304–317

    Article  CAS  PubMed  Google Scholar 

  14. Xu XJ, Shen L, Yang YP, et al. Serum β-catenin levels associated with the ratio of RANKL/OPG in patients with postmenopausal osteoporosis. Int J Endocrinol, 2013,2013:534 352

    Google Scholar 

  15. Albers J, Keller J, Baranowsky A, et al. Canonical Wnt signaling inhibits o-steoclastogenesis independent of osteoprotegerin. J Cell Biol, 2013,200(4):537–549

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell, 2012,149(6):1192–1205

    Article  CAS  PubMed  Google Scholar 

  17. Essers MA, de Vries-Smits LM, Barker N, et al. Functional interaction between beta-catenin and FOXO in oxdative stress signaling. Science, 2005,308(5725):1181–1184

    Article  CAS  PubMed  Google Scholar 

  18. 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):383–388

    Article  CAS  PubMed  Google Scholar 

  19. Drake MT, Srinivasan B, Mödder UI, et al. Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women. J Clin Endocrinol Metab, 2010,95(11):5056–5062

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Xu XJ, Shen L, Yang YP, et al. Serum sclerostin levels associated with lumbar spine bone mineral density and bone turnover markers in patients with postmenopausal osteoporosis. Chin Med J, 2013,126(13):2480–2484

    CAS  PubMed  Google Scholar 

  21. Kyvernitakis I, Rachner TD, Urbschat A, et al. Effect of aromatase inhibition on serum levels of sclerostin and dickkopf-1, bone turnover markers and bone mineral density in women with breast cancer. J Cancer Res Clin Oncol, 2014,140(10):1671–1680

    Article  CAS  PubMed  Google Scholar 

  22. Voorzanger-Rousselot N, Journe F, Doriath V, et al. Assessment of circulating dickkopf-1 with a new two-site immunoassay in healthy subjects and women with breast cancer and bone metastases. Calcifi Tissue Int, 2009,84(5):348–354

    Article  CAS  Google Scholar 

  23. Anastasilakis AD, Polyzos SA, Avramidis A, et al. The effect of teriparatide on serum Dickkopf-1 levels in postmenopausal women with established osteoporosis. Clin Endocrinol (Oxf), 2010,72(6):752–757

    Article  CAS  Google Scholar 

  24. Bafico A, Liu GZ, Yaniv A, et al. Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. Nat Cell Biol, 2001,3(7):683–686

    Article  CAS  PubMed  Google Scholar 

  25. Davidson G, Mao BY, Barrantes ID, et al. Kremen proteins interact with Dickkopf1 to regulate anteroposterior CNS patterning. Development, 2002,129(24):5587–5596

    Article  CAS  PubMed  Google Scholar 

  26. Gregory CA, Singh H, Perry AS, et al. The Wnt signaling inhibitor dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow. J Biol Chem, 2003,278(30):28 067–28 078

    Article  CAS  Google Scholar 

  27. Chu EY, Hens J, Andl T, et al. Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development, 2004,131(19):4819–4829

    Article  CAS  PubMed  Google Scholar 

  28. Kuhnert F, Davis CR, Wang HT, et al. Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1. Proc atl Acad Sci USA, 2004,101(1):266–271

    Article  CAS  Google Scholar 

  29. Voskaridou E, Christoulas D, Xirakia C, et al. Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid administration. Haematologica, 2009,94(5):725–728

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Aguilera O, Peña C, García JM, et al. The Wnt antagonist DICKKOPF-1 gene is induced by 1alpha,25-dihyroxy vitamin D3 associated to the differentiation of human colon cancer cells. Carcinogenesis, 2007,28(9):1877–1884

    Article  CAS  PubMed  Google Scholar 

  31. Glass DA 2nd, Karsenty G. Canonical Wnt signalin-in osteoblasts is required for osteoclast differentiation. Ann New York Acad Sci, 2006,1068:117–130

    Article  CAS  Google Scholar 

  32. Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nature Med, 2007,13(2):156–163

    Article  CAS  PubMed  Google Scholar 

  33. Bellido T, Ali AA, Gubrij I, et al. Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology, 2005,146(11):4577–4583

    Article  CAS  PubMed  Google Scholar 

  34. Guo J, Liu M, Yang D, et al. Suppression of Wnt signaling by Dkk1 attenuates PTH-mediated stromal cell response and new bone formation. Cell Metab, 2010,11(2):161–171

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Integrated Traditional Chinese Medicine and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Jun Tian  (田 峻), Xiao-juan Xu  (徐晓娟), Lin Shen  (沈 霖), Yan-ping Yang  (杨艳萍), Rui Zhu  (朱 锐), Bo Shuai  (帅 波), Xi-Wen Zhu  (朱习文), Cheng-gang Li  (李成刚), Chen Ma  (马 陈) & Lin Lv  (吕 林)

  2. Department of Rehabilitation Medicine, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China

    Jun Tian  (田 峻)

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  1. Jun Tian  (田 峻)
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Correspondence to Lin Shen  (沈 霖).

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The authors contributed equally to this work.

This project was supported by grants from National Natural Science Foundation of China (No. 81473492 and No. 81273907), and Health Department of Hubei Province, China (No. 2012Z-Z01).

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Tian, J., Xu, Xj., Shen, L. et al. Association of serum Dkk-1 levels with β-catenin in patients with postmenopausal osteoporosis. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 35, 212–218 (2015). https://doi.org/10.1007/s11596-015-1413-6

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  • DOI: https://doi.org/10.1007/s11596-015-1413-6

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