Skip to main content

Advertisement

SpringerLink
Log in

Decreased Expression of Heat Shock Protein 47 Is Associated with T-2 Toxin and Low Selenium-Induced Matrix Degradation in Cartilages of Kashin-Beck Disease

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

Abstract

Recent evidence suggests a role of type II collagen in Kashin-Beck disease (KBD) degeneration. We aimed to assess the abnormal expression of heat shock protein 47 (HSP47) which is associated with a decrease in type II collagen and an increase in cartilage degradation in KBD. Hand phalange cartilages were collected from KBD and healthy children. Rats were administered with T-2 toxin under the selenium (Se)-deficient diet. ATDC5 cells were seeded on bone matrix gelatin to construct engineered cartilaginous tissue. C28/I2 and ATDC5 cells and engineered tissue were exposed to different concentrations of T-2 toxin with or without Se. Cartilage degeneration was determined through histological evaluation. The distribution and expression of type II collagen and HSP47 were investigated through immunohistochemistry, western blotting, and real-time PCR. KBD cartilages showed increased chondronecrosis and extracellular matrix degradation in deep zone with decreased type II collagen and HSP47 expression. The low-Se + T-2 toxin animal group showed a significantly lower type II collagen expression along with decreased HSP47 expression. Decreased type II collagen and HSP47 in C28/I2 and ATDC5 cells induced by T-2 toxin showed a dose-dependent manner. Hyaline-like cartilage with zonal layers was developed in engineered cartilaginous tissues, with decreased type II collagen and HSP47 expression found in T-2 toxin-treated group. Se-supplementation partially antagonized the inhibitory effects of T-2 toxin in chondrocytes and cartilages. HSP47 plays a role in the degenerative changes of KBD and associated with T-2 toxin-induced decreased type II collagen expression, further promoting matrix degradation.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Allander E (1994) Kashin-Beck disease. An analysis of research and public health activities based on a bibliography 1849-1992. Scand J Rheumatol Suppl 99:1–36. https://doi.org/10.3109/03009749409117126

    Article  CAS  PubMed  Google Scholar 

  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 22:1774–1783. https://doi.org/10.1016/j.joca.2014.07.023

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  4. Huang Q, Zhou ZK, Ma J, Li Y, Yang X, Shen B, Yang J, Kang PD, Pei FX (2015) The arthropathic and functional impairment features of adult Kashin-Beck disease patients in Aba Tibetan area in China. Osteoarthr Cartil 23:601–606. https://doi.org/10.1016/j.joca.2015.01.005

    Article  CAS  Google Scholar 

  5. Song QQ, Liu H, Lian W, Wang Y, Sun LY, Gao M, Liu YQ, Deng HX, Deng Q, Liu N, Yu J (2018) The characteristics of positive and confusing hand X-ray signs in diagnosing Kashin-Beck disease in children in Chiina. Sci Rep 8:3277. https://doi.org/10.1038/s41598-018-21675-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhang GQ, Liu JX, Yu JY, Shi YX, Zhang SJ (1989) Ultrastructure of chondrocytes in articular cartilage of Kashin-Beck disease. Chin J Endemiol 8:27–30

    Google Scholar 

  7. Zhang Y, He Y, Zhang D, Zhang M, Wang MY, Zhang Y, Ma T, Chen J (2018) Death of chondrocytes in Kashin-Beck disease: apoptosis, necrosis or necroptosis? Int J Exp Pathol 99:312–322. https://doi.org/10.1111/iep.12297

    Article  CAS  PubMed  Google Scholar 

  8. Wang KW, Yu J, Liu H, Liu YQ, Liu N, Cao Y, Zhang X, Sun D (2020) Endemic Kashin-Beck disease: a food-sourced osteoarthropathy. Semin Arthritis Rheum 50:366–372. https://doi.org/10.1016/j.semarthrit.2019.07.014

    Article  CAS  PubMed  Google Scholar 

  9. Guo YN, Li HR, Yang LS, Li YH, Wei BG, Wang WY et al (2017) Trace element levels in scalp hair of school children in Shigase, Tibet, an endemic area for Kashin-Beck disease(KBD). Biol Trace Elem Res 180:15–22. https://doi.org/10.1007/s12011-017-0988-0

    Article  CAS  PubMed  Google Scholar 

  10. Chen JH, Xue S, Li S, Wang ZL, Yang H, Wang W, Song D, Zhou X, Chen C (2012) Oxidant damage in Kashin-Beck disease and a rat Kashin-Beck disease model by employing T-2 toxin treatment under selenium deficient conditions. J Orthop Res 30:1229–1237. https://doi.org/10.1002/jor.22073

    Article  CAS  PubMed  Google Scholar 

  11. Guan F, Li S, Wang ZL, Yang H, Xue S, Wang W, Song D, Zhou X, Zhou W, Chen JH, Caterson B, Hughes C (2013) Histopathology of chondronecrosis development in knee articular cartilage in a rat model of Kashin-Beck disease using T-2 toxin and selenium deficiency conditions. Rheumatol Int 33:157–166. https://doi.org/10.1007/s00296-011-2335-7

    Article  CAS  PubMed  Google Scholar 

  12. Song QQ, Sun LY, Li CH, Liu YJ, Cui SL, Liu YQ, Cao YH, Pei JR, Wang Y, Lian W, Jiao Z, Deng Q, Yu J (2019) The urinary levels of CTX- II, C2C, PYD, and helix-II increased among adults with KBD: a cross-sectional study. J Orthop Surg Res 14:328. https://doi.org/10.1186/s13018-019-1392-6

    Article  PubMed  PubMed Central  Google Scholar 

  13. Chang Y, Wang X, Sun Z, Jin Z, Chen M, Wang X, Lammi MJ, Guo X (2017) Inflammatory cytokine of IL-1β is involved in T-2 toxin-triggered chondrocyte injury and metabolism imbalance by the activation of Wnt/β-catenin signaling. Mol Immunol 91:195–201. https://doi.org/10.1016/j.molimm.2017.08.019

    Article  CAS  PubMed  Google Scholar 

  14. Chen JH, Luo MX, Wang W, Zhang ZT, He Y, Duance VC et al (2015) Altered proteolytic activity and expression of MMPs and aggrecanases and their inhibitors in Kashin-Beck disease. J Orthop Res 33:47–55. https://doi.org/10.1002/jor.22708

    Article  CAS  PubMed  Google Scholar 

  15. Wang W, Guo X, Chen JH, Xu P, Lammi MJ (2008) Morphology and phenotype expression of types I, II, III, and X collagen and MMP-13 of chondrocytes cultured from articular cartilage of Kashin-Beck disease. J Rheumatol 35:696–702

    PubMed  Google Scholar 

  16. Zhou X, Yang H, Guan F, Xue S, Song D, Chen J, Wang Z (2015) T-2 toxin alters the levels of collagen II and its regulatory enzymes MMPs/TIMP-1 in a low-selenium rat model of Kashin-Beck disease. Biol Trace Elem Res 169:237–246. https://doi.org/10.1007/s12011-015-0408-2

    Article  CAS  PubMed  Google Scholar 

  17. Ito S, Nagata K (2018) Roles of the endoplasmic reticulum–resident, collagen-specific molecular chaperone Hsp47 in vertebrate cells and human disease. J Biol Chem 294:2133–2141. https://doi.org/10.1074/jbc.tm118.002812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ito S, Nagata K (2017) Biology of Hsp47 (Serpin H1), a collagen-specific molecular chaperone. Semin Cell Dev Biol 62:142–151. https://doi.org/10.1016/j.semcdb.2016.11.005

    Article  CAS  PubMed  Google Scholar 

  19. Nagata K (2003) HSP47 as a collagen-specific molecular chaperone: function and expression in normal mouse development. Semin Cell Dev Biol 14:275–282. https://doi.org/10.1016/j.semcdb.2003.09.020

    Article  CAS  PubMed  Google Scholar 

  20. Matsuoka Y, Kubota H, Adachi E, Nagai N, Marutani T, Hosokawa N, Nagata K (2004) Insufficient folding of type IV collagen and formation of abnormal basement membrane-like structure in embryoid bodies derived from Hsp47-null embryonic stem cells. Mol Biol Cell 15:4467–4475. https://doi.org/10.1091/mbc.e04-01-0050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Masago Y, Hosoya A, Kawasaki K, Kawano S, Nasu A, Toguchida J, Fujita K, Nakamura H, Kondoh G, Nagata K (2012) The molecular chaperone Hsp47 is essential for cartilage and endochondral bone formation. J Cell Sci 125:1118–1128. https://doi.org/10.1242/jcs.089748

    Article  CAS  PubMed  Google Scholar 

  22. Chioran A, Duncan S, Catalano A, Brown TJ, Ringuette MJ (2017) Collagen IV trafficking: the inside-out and beyond story. Dev Biol 431:124–133. https://doi.org/10.1016/j.ydbio.2017.09.037

    Article  CAS  PubMed  Google Scholar 

  23. Sengupta P (2013) The laboratory rat: relating its age with Human’s. Int J Prev Med 4:624–630

    PubMed  PubMed Central  Google Scholar 

  24. Reeves PG (1997) Components of the AIN-93 diets as improvements in the AIN-76A diet. J Nutr 127:838S–841S. https://doi.org/10.1093/jn/127.5.838S

    Article  CAS  PubMed  Google Scholar 

  25. Carballo CB, Nakagawa Y, Sekiya I, Rodeo SA (2017) Basic science of articular cartilage. Clin Sports Med 36:413–425. https://doi.org/10.1016/j.csm.2017.02.001

    Article  PubMed  Google Scholar 

  26. Evans HB, Ayad S, Abedin MZ, Hopkins S, Morgan K, Walton KW, Weiss JB, Holt PJ (1983) Localisation of collagen types and fibronectin in cartilage by immunofluorescence. Ann Rheum Dis 42:575–581. https://doi.org/10.1136/ard.42.5.575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Eyre DR (2004) Collagens and cartilage matrix homeostasis. Clin Orthop Relat Res 427:S118–S122. https://doi.org/10.1097/01.blo.0000144855.48640.b9

    Article  Google Scholar 

  28. Garnero P, Ayral X, Rousseau JC, Christgau S, Sandell LJ, Dougados M, Delmas PD (2002) Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis. Arthritis Rheum 46:2613–2624. https://doi.org/10.1002/art.10576

    Article  CAS  PubMed  Google Scholar 

  29. Wang XX, Cai L (2018) Expression level of proteoglycan, collagen and type II collagen in osteoarthritis rat model is promoted and degradation of cartilage is prevented by glucosamine methyl ester. Eur Rev Med Pharmacol Sci 22:3609–3616. https://doi.org/10.26355/eurrev_201806_15188

    Article  PubMed  Google Scholar 

  30. Alam J, Jantan I, Kumolosasi E, Nafiah MA, Mesaik MA (2018) Suppressive effects of the standardized extract of Phyllanthus amarus on type II collagen-induced rheumatoid arthritis in Sprague Dawley rats. Curr Pharm Biotechnol 19:1156–1169. https://doi.org/10.2174/1389201020666181211124954

    Article  CAS  PubMed  Google Scholar 

  31. Firner S, Zaucke F, Michael J, Dargel J, Schiwy-Bochat KH, Heilig J, Rothschild MA, Eysel P, Brüggemann GP, Niehoff A (2017) Extracellular distribution of collagen II and perifibrillar adapter proteins in healthy and osteoarthritic human knee joint cartilage. J Histochem Cytochem 65:593–606. https://doi.org/10.1369/0022155417729154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cheng B, Zhang Y, Tong B, Yin H (2017) Influence of selenium on the production of T-2 toxin by Fusarium poae. Biol Trace Elem Res 178:147–152. https://doi.org/10.1007/s12011-016-0900-3

    Article  CAS  PubMed  Google Scholar 

  33. Khan ES, Sankaran S, Paez JI, Muth C, Han MKL, del Campo A (2019) Photoactivatable Hsp47: a tool to regulate collagen secretion and assembly. Adv Sci 6(9):1801982. https://doi.org/10.1002/advs.201801982

    Article  CAS  Google Scholar 

  34. Marutani T, Yamamoto A, Nagai N, Kubota H, Nagata K (2004) Accumulation of type IV collagen in dilated ER leads to apoptosis in Hsp47-knockout mouse embryos via induction of CHOP. J Cell Sci 117:5913–5922

    Article  CAS  Google Scholar 

  35. Li X, Jin L, Balian G, Laurencin CT, Greg Anderson D (2006) Demineralized bone matrix gelatin as scaffold for osteochondral tissue engineering. Biomaterials 27:2426–2433. https://doi.org/10.1016/j.biomaterials.2005.11.040

    Article  CAS  PubMed  Google Scholar 

  36. Pei Y, Fan JJ, Zhang XQ, Zhang ZY, Yu M (2014) Repairing the osteochondral defect in goat with the tissue-engineered osteochondral graft preconstructed in a double-chamber stirring bioreactor. Biomed Res Int 2014:219203–219211. https://doi.org/10.1155/2014/219203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Nagai N, Hosokawa M, Itohara S, Adachi E, Matsushita T, Hosokawa N, Nagata K (2000) Embryonic lethality of molecular chaperone hsp47 knockout mice is associated with defects in collagen biosynthesis. J Cell Biol 150:1499–1506. https://doi.org/10.1083/jcb.150.6.1499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by the National Natural Science Foundation of China (No. 81872565, No. 81573102, No. 81273006).

Author information

Author notes

  1. Meng Zhang and Mengying Wang contributed equally to this work.

Authors and Affiliations

  1. School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases in National Health Commission of PR of China, Xi’an Jiaotong University, Xi’an, Shaanxi, China

    Meng Zhang, Mengying Wang, Hui Wang, Ying Zhang, Zhengzheng Li, Yiping Feng, Yinan Liu, Yue Liu, Yucheng Liao, Wenjun Wang, Qian Fang & Jinghong Chen

  2. The Institute of Endemic Diseases, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    Jinghong Chen

Authors
  1. Meng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mengying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhengzheng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yiping Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yinan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yue Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yucheng Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wenjun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Qian Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jinghong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jinghong Chen.

Ethics declarations

Conflict of Interests

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

ESM 1

(PDF 139 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, M., Wang, M., Wang, H. et al. Decreased Expression of Heat Shock Protein 47 Is Associated with T-2 Toxin and Low Selenium-Induced Matrix Degradation in Cartilages of Kashin-Beck Disease. Biol Trace Elem Res 199, 944–954 (2021). https://doi.org/10.1007/s12011-020-02237-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-020-02237-1

Keywords

Search

Navigation