Skip to main content

Advertisement

SpringerLink
Log in

Zinc: the Other Suspected Environmental Factor in Kashin-Beck Disease in Addition to Selenium

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Kashin-Beck disease (KBD) is an endemic chronic osteochondral disease characterized by high prevalence, disability, and morbidity and is distributed from the northeast to the southwest in China, in some regions of Eastern Siberia in Russia, and in North Korea. Although the selenium deficiency etiological hypothesis for KBD has been proposed by scientists for decades, the idea that selenium deficiency is one of the most important environmental factors but not the primary and sole pathogenic factor for KBD has been widely accepted. Zn2+, which is closely involved in the synthesis of enzymes, nucleic acids, and proteins, is an essential microelement in vivo. A conundrum still exists in research on the relationship between Zn2+ and KBD due to inconsistent results, but it has been confirmed that Zn2+ can help repair metaphyseal lesions in patients with KBD, indicating that Zn2+ might play a key role in the pathogenesis of KBD, although the mechanism is unknown. The zinc-ZIP8-MTF1 axis in chondrocytes forms a catabolic cascade that promotes upregulation of the crucial effector matrix-degrading enzymes MMP3, MMP13, and ADAMTS5, thereby leading to osteoarthritis (OA) cartilage destruction. Zinc finger protein-related genes, the ZNT family, and the ZIP family of Zn2+ transporter genes have been found to be differentially expressed in KBD by high-throughput screening. Therefore, Zn2+ could play a key role in the pathogenesis of KBD.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. P.R.China Ministry of Health (2012) The prevention and control status of Kaschin-Beck disease in 2011. Available at: http://www.nhfpcgovcn/htmlfiles/zwgkzt/ptjnj/year2012/index2012html

  2. Guo X, Ma WJ, Zhang F, Ren FL, Qu CJ, Lammi MJ (2014) Recent advances in the research of an endemic osteochondropathy in China: Kashin-Beck disease. Osteoarthr Cartil 22(11):1774–1783. doi:10.1016/j.joca.2014.07.023

    Article  CAS  PubMed  Google Scholar 

  3. Xiong G (2001) Diagnostic, clinical and radiological characteristics of Kashin-Beck disease in Shaanxi Province, PR China. Int Orthop 25(3):147–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kong Y, Pubu C, Wang J, Jiangcu Q, Zewang G, Duzhu S (2014) To investigate and analyze the condition of Kashin-Beck disease around 7–12 years old children in Bianba county of Tibet in 2013. Chin J Ctrl Endem Dis 29(5):350–351

    Google Scholar 

  5. Peng A, Yang C, Rui H, Li H (1992) Study on the pathogenic factors of Kashin-Beck disease. J Toxicol Environ Health 35(2):79–90. doi:10.1080/15287399209531597

    Article  CAS  PubMed  Google Scholar 

  6. Guo X, Shiyuan Z, Dongxu M (1992) The role of low selenium in occurence of Kashin-Beck Disese. J Xi’ an M ED UN IV (S) 4(2):99–108

    Google Scholar 

  7. Dongxu M (1986) Pathology of selenium deficiency in Kashin-Beck disease. In: Selenium in Biology and Medicine. No strand Reinhold Company, New York

  8. Dongxu M, Dexiu D, Zhilun W (1997) Study on relationship between selenium and Kashin-Beck disease in 20 years. Chinese J Control Endem Dis 12(1):18–21

    Google Scholar 

  9. Dongxu M, Lu S, Chai B (1990) Progress of the relationship between low selenium and Kashin-Beck disease. Chinese J of Endemic 9(2):119–121

    Google Scholar 

  10. Guo X, Dexiu D, Wang Z, Lu S, Guo J, Tan X, Dong G, Peipu Y, Ma C, Wenxin C, Wenzhen H (1999) A study on the reparative action of X-ray lesions in metaphyses and distal end of bone in children’s fingers with Kashin-Beck disease treated by Se-fortified wheat. Chinese J of Control of Endemic Diseases 9:118–120

    Google Scholar 

  11. Fukada T, Yamasaki S, Nishida K, Murakami M, Hirano T (2011) Zinc homeostasis and signaling in health and diseases: zinc signaling. Journal of biological inorganic chemistry: JBIC: a publication of the Society of Biological Inorganic Chemistry 16(7):1123–1134. doi:10.1007/s00775-011-0797-4

    Article  CAS  Google Scholar 

  12. Zhang S, Guo X, Li S, Wang H (1988) The relationship between zinc and Kashin-Beck disease. Chinese Journal of Control of Endemic Disenaces 3(4):238–239

    Google Scholar 

  13. Bai C, Lv S, Wang Z (1994) Determination of hair zinc contents in children from Kashin-Beck endemic area in Shaanxi province. Chinese Journal of Endemiology 13(5):281–282

    Google Scholar 

  14. Huang P, Yang G, Cui C, Wang S (1996) Comparative analysis zinc content in children aged 7–12 with Kashin Beck disease in ten years. Henan journal of preventive medicine 7(5):285–286

    Google Scholar 

  15. Lei Y, Xu G, Yang Y (1996) Comparative detection of hair Cu, Zn, Fe, Mn contents of children from Keshan disease and Kashin-Beck disease co-existing endemic area. Journal of Xi’an Medical University 17(2):163–164

    CAS  Google Scholar 

  16. Yu Z (1993) Determination of zinc content in Qinling Mountain KBD endemic areas. Chinese Journal of Endemiology 2:111–113

    Google Scholar 

  17. Yu Z (1993) Determination of Zn concentration in Kashin-Beck disease affected areas. Endemic Diseases Bulletin 8(1):35–37

    Google Scholar 

  18. Wang S (1992) Analysis of Zn contents in the water, soil and children’s hair in Kashin-Beck disease areas of Shanxi Province. Endemic Diseases Bulletin 3(7):131–132

    Google Scholar 

  19. Wang Z, He F, Gao B, Zhang X, Yang J (1989) A case-control study in Kashin-Beck disease. Journal of Harbin Medical University 23(5):57–59

    Google Scholar 

  20. Bai C, Lv S, Wang Z, Xue L (1995) Studies on zinc nutritional status of children from Kashin-Beck disease affected areas. Chinese Journal of Control of Endemic Disenaces 10(1):7–8

    Google Scholar 

  21. Cai Bai, Shemin Lv, Zhilun Wang, Xue L (1995) Analyses of zinc contents in sera and hairs of children from Kashin-Beck disease affected areas in the north region of WeiHe River in Shaanxi Province. Journal of Xi’an Medical University 16 (4)

  22. Liu L, Zhao X, Ming D, Ma W (2014) Analysis of 18 kinds of elements in blood of patients with Kashin-Beck disease in parts of Aba autonomous prefecture, Sichuan. J Environ Health 31(7):587-589

  23. Yang C, Yang Z, Zhuoma BS, Ruodeng XR, Ciwang BM, Shengcheng Z, Zhu ZS (2013) Correlations between diet structure and serum indicators among population in Kashin-Beck disease area in Tibet. Chin J Public Health 29(1):122-125

  24. Lu G, Jin M, Lei S (2004) Relationship between Kashin-Beck disease in children and trace elements and clinical significance. Chin J Endemiol 23(6):596-599

  25. Sun G, Xiong C, Zhang Y, Wang S, Xie Y, Wang H,Shi N, Wang J (2004) Comparative analysis of the inorganic elements in wheats collected from Kashin-Beck disease(KBD)area and non-KBD area. Studies of Trace Elements and Health 21(3):23-25

  26. Bai C, Zhang S, Yu Z, Xiong Y, Xue L, Li Y, Fan W (1990) Contrastive analyses on content of some inorganic elements in wheat flour, maize flour and soybean in Kashin-Beck disease areas. Chin J Endemiol 9(2):83-86

  27. Yang J (1985) Study on the ecological environment of Kaschin Beck disease in Yongshou County in Shaanxi province. Acta Sci Circumst 5(1):1–19

    CAS  Google Scholar 

  28. Li C, Zhang S (1988) A study of the relationship between zinc and Kashin-Beck disease. Chinese Journal of endemic diseases 7(5):279–280

    Google Scholar 

  29. Jia B, Zhang Q, Jiang Z, Wei L, Yang S (1992) The relationship between zinc and Kashin-Beck disease. Chinese Community Doctors 2:45–46

    Google Scholar 

  30. Wang WZ, Guo X, Duan C, Ma WJ, Zhang YG, Xu P, Gao ZQ, Wang ZF, Yan H, Zhang YF, Yu YX, Chen JC, Lammi MJ (2009) Comparative analysis of gene expression profiles between the normal human cartilage and the one with endemic osteoarthritis. Osteoarthr Cartil 17(1):83–90. doi:10.1016/j.joca.2008.05.008

    Article  CAS  PubMed  Google Scholar 

  31. Wang S, Guo X, Wu XM, Lammi MJ (2012) Genome-wide gene expression analysis suggests an important role of suppressed immunity in pathogenesis of Kashin-Beck disease. PLoS One 7(1):e28439. doi:10.1371/journal.pone.0028439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Parraga G, Horvath SJ, Eisen A, Taylor WE, Hood L, Young ET, Klevit RE (1988) Zinc-dependent structure of a single-finger domain of yeast ADR1. Science 241(4872):1489–1492

    Article  CAS  PubMed  Google Scholar 

  33. Lepage LM, Giesbrecht JA, Taylor CG (1999) Expression of T lymphocyte p56(lck), a zinc-finger signal transduction protein, is elevated by dietary zinc deficiency and diet restriction in mice. J Nutr 129(3):620–627

    CAS  PubMed  Google Scholar 

  34. Chen J, Luo M, Wang W, Zhang Z, He Y, Duance VC, Hughes CE, Caterson B, Cao J (2015) Altered proteolytic activity and expression of MMPs and aggrecanases and their inhibitors in Kashin-Beck disease. Journal of orthopaedic research: official publication of the Orthopaedic Research Society 33(1):47–55. doi:10.1002/jor.22708

    Article  CAS  Google Scholar 

  35. Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8(3):221–233. doi:10.1038/nrm2125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kim JH, Jeon J, Shin M, Won Y, Lee M, Kwak JS, Lee G, Rhee J, Ryu JH, Chun CH, Chun JS (2014) Regulation of the catabolic cascade in osteoarthritis by the zinc-ZIP8-MTF1 axis. Cell 156(4):730–743. doi:10.1016/j.cell.2014.01.007

    Article  CAS  PubMed  Google Scholar 

  37. Wang X, Ning Y, Tan W, Yu H, Li Z, Guo X (2016) Population-based comparative analysis of differentially expressed genes between Kashin-Beck disease grades I and II. Scand J Rheumatol 45(3):230–235. doi:10.3109/03009742.2015.1058416

    Article  PubMed  Google Scholar 

  38. Prasad AS (1995) Zinc: an overview. Nutrition 11(1 Suppl):93–99

    CAS  PubMed  Google Scholar 

  39. Cousins RJ, Liuzzi JP, Lichten LA (2006) Mammalian zinc transport, trafficking, and signals. J Biol Chem 281(34):24085–24089. doi:10.1074/jbc.R600011200

    Article  CAS  PubMed  Google Scholar 

  40. Liuzzi JP, Lichten LA, Rivera S, Blanchard RK, Aydemir TB, Knutson MD, Ganz T, Cousins RJ (2005) Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proceedings of the National Academy of Sciences of the United States of America 102 (19):6843–6848. doi:10.1073/pnas.0502257102

  41. Kitamura H, Morikawa H, Kamon H, Iguchi M, Hojyo S, Fukada T, Yamashita S, Kaisho T, Akira S, Murakami M, Hirano T (2006) Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. Nat Immunol 7(9):971–977. doi:10.1038/ni1373

    Article  CAS  PubMed  Google Scholar 

  42. Kury S, Dreno B, Bezieau S, Giraudet S, Kharfi M, Kamoun R, Moisan JP (2002) Identification of SLC39A4, a gene involved in acrodermatitis enteropathica. Nat Genet 31(3):239–240. doi:10.1038/ng913

    Article  PubMed  Google Scholar 

  43. Ovesen J, Moller-Madsen B, Nielsen PT, Christensen PH, Simonsen O, Hoeck HC, Laursen MB, Thomsen JS (2009) Differences in zinc status between patients with osteoarthritis and osteoporosis. J Trace Elem Med Biol 23(1):1–8. doi:10.1016/j.jtemb.2008.12.001

    Article  CAS  PubMed  Google Scholar 

  44. Roschger A, Hofstaetter JG, Pemmer B, Zoeger N, Wobrauschek P, Falkenberg G, Simon R, Berzlanovich A, Thaler HW, Roschger P, Klaushofer K, Streli C (2013) Differential accumulation of lead and zinc in double-tidemarks of articular cartilage. Osteoarthr Cartil 21(11):1707–1715. doi:10.1016/j.joca.2013.06.029

    Article  CAS  PubMed  Google Scholar 

  45. Lee M, Won Y, Shin Y, Kim JH, Chun JS (2016) Reciprocal activation of hypoxia-inducible factor (HIF)-2alpha and the zinc-ZIP8-MTF1 axis amplifies catabolic signaling in osteoarthritis. Osteoarthr Cartil 24(1):134–145. doi:10.1016/j.joca.2015.07.016

    Article  CAS  PubMed  Google Scholar 

  46. Kim HE, Rhee J, Park S, Yang J, Chun JS (2016) Upregulation of Atrogin-1/FBXO32 is not necessary for cartilage destruction in mouse models of osteoarthritis. Osteoarthr Cartil. doi:10.1016/j.joca.2016.07.008

    PubMed Central  Google Scholar 

  47. Choi WS, Chun JS (2016) Upregulation of lipocalin-2 (LCN2) in osteoarthritic cartilage is not necessary for cartilage destruction in mice. Osteoarthr Cartil. doi:10.1016/j.joca.2016.07.009

    Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China [grant number 81472924 and 81620108026] and the Fundamental Research Funds for the Central Universities.

Author information

Authors and Affiliations

  1. School of Public Health, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an Jiaotong University Health Science Center, No.76 Yanta West Road, Xi’an, Shaanxi, 710061, People’s Republic of China

    Xi Wang, Yujie Ning, Lei Yang, Fangfang Yu & Xiong Guo

Authors
  1. Xi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yujie Ning
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fangfang Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiong Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiong Guo.

Additional information

Xi Wang and Yujie Ning contributed equally to this work

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, X., Ning, Y., Yang, L. et al. Zinc: the Other Suspected Environmental Factor in Kashin-Beck Disease in Addition to Selenium. Biol Trace Elem Res 179, 178–184 (2017). https://doi.org/10.1007/s12011-017-0964-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-017-0964-8

Keywords

Search

Navigation