The expression of p-ATF2 involved in the chondeocytes apoptosis of an endemic osteoarthritis, Kashin-Beck disease

BMC Musculoskeletal Disorders

Mikko J Lammi³  Peng Xu¹  Weizhuo Wang⁴  Jiangtao Liu²  Feng Zhang²  Wuhong Tan²  Xiong Guo²  Jing Han² 

[1] Department of Orthopaedics Surgery, The Xi’an Red Cross Hospital, 710054 Xi’an, Shaanxi, PR China;Faculty of Public Health, College Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi’an Jiaotong University, 710061 Xi’an, Shaanxi, PR China;Department of Biosciences, Applied Biotechnology, University of Kuopio, Bioteknia 2, 70211, Kuopio, Finland;Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine,Xi’an Jiaotong University, 710061 Xi’an, Shaanxi, PR China

关键词: Kashin-Beck disease;    Cartilage;    Chondrocytes;    Apoptosis;    ATF2;    JNK and p38 pathways;   

Others  :  1130283
DOI  :  10.1186/1471-2474-14-209

 received in 2012-12-27, accepted in 2013-07-11,  发布年份 2013

【 摘 要 】

Background

The purpose of the study was to understand the function and expression of ATF2 by JNK and p38 signal pathways in the chondrocytes apoptosis of articular cartilage of the Kashin-Beck disease (KBD).

Methods

The changes of ATF2, JNK and p38 mRNAs and proteins were investigated between cartilage and chondrocyte as well as KBD and normal. JNK and p38 inhibitors were used as treatments to prevent apoptosis in chondrocytes from KBD patients.

Results

It was found that the protein levels of p-p38, p-JNK, ATF2 and p-ATF2 increased in KBD human cartilage which is in line with the higher mRNA levels of p38, JNK and ATF2 as compared both with normal cartilage and KBD chondrocytes. In addition, p-ATF2 was only detected in KBD cartilage. Furthermore, JNK inhibitor was more effective than p38 inhibitor in preventing chondrocyte apoptosis at equal concentrations of 10 μM.

Conclusion

These findings indicated the expression of p-ATF2 by JNK and p38 signal pathways involved in the chondrocyte apoptosis in cartilage with KBD.

【 授权许可】

   
2013 Han et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]National Kashin-Beck Disease Surveillance Group: Report of a national survey of Kashin-Beck disease prevalence in 2005. Chin J Endemiol 2006, 25:670-672.
• [2]China Ministry of Health statistics and information center: Prevention and control of endemic diseases. 2010. [China Health Statistics Annual Report] http://www.moh.gov.cn/htmlfiles/zwgkzt/ptjnj/year2011/index2011.html webcite
• [3]Yamamuro T: Kashin-Beck disease: a historical overview. Int Orthop 2001, 25:134-137.
• [4]Guo X: Progression and prospect of etiology and pathogenesis of Kashin-Beck disease in China. Chin J Endemiol 2008, 27:6-8.
• [5]Zou K, Liu G, Wu T, et al.: Selenium for preventing Kashin-Beck osteoarthropathy in children: a meta-analysis. Osteoarthr Cartilage 2009, 17:144-151.
• [6]Ren FL, Guo X, Zhang RJ, et al.: Effects of selenium and iodine deficiency on bone, cartilage growth plate and chondrocyte differentiation in two generations of rats. Osteoarthr Cartilage 2007, 15:1171-1177.
• [7]Peng A, Wang WH, Wang CX, et al.: The role of humic substances in drinking water in Kashin-Beck disease in China. Environ Health Persp 1999, 107:293-296.
• [8]Guo X, Zhang SY, Mo DX: A role of low selenium in the occurrence of Kashin-Beck disease. J Xi’an Jiaotong Univ (Med Sci) 1992, 4:99-108.
• [9]Tan JA, Zhu WY, Wang WY, et al.: Selenium in soil and endemic diseases in China. Sci Total Environ 2002, 284:227-235.
• [10]Yang CL, Niu CR, Bodo M, et al.: Fulvic acid supplementation and selenium deficiency disturb the structural integrity of mouse skeletal tissue: an animal model to study the molecular defects of Kashin-Beck disease. Biochem J 1993, 289:829-835.
• [11]Li XY, Guo X, Wang LX, et al.: Serum hyaluronic acid, tumor necrosis factor-a, vascular endothelial growth factor, NO, and Se levels in adult patients with Kashin-Beck disease. J South Med Univ 2007, 27:941-944.
• [12]Wang W, Guo X, Chen JC, et al.: 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 2008, 35:696-702.
• [13]Mo DX: Electron microscope of Kashin-Beck patients with articular cartilage and epiphyseal cartilage chondrocytes. J Xi’an Jiaotong Univ (Med Sci) 1979, 3:34-39.
• [14]Wang S, Guo X, Wu XM, et al.: Genome-wide gene expression analysis suggests immunity in pathogenesis of Kashin-Beck disease. PLoS One 2012, 7:e28439.
• [15]China Ministry of Public Health: Diagnosis of Kaschin-Beck disease. http://www.moh.gov.cn/zwgkzt/s9500/201006/47920/files/810f8a8b47cf434195a59c071a97bdc0.pdf webcite
• [16]Raman M, Chen W, Cobb MH: Differential regulation and properties of MAPKs. Oncogene 2007, 26:3100-3112.
• [17]Kumar S, Boehm J, Lee JC: p38 MAP kinases: key signaling molecules as therapeutic targets for inflammatory diseases. Nat Rev Drug Discov 2003, 2:717-726.
• [18]Dhanasekaran DN, Reddy EP: JNK signaling in apoptosis. Oncogene 2008, 27:6245-6251.
• [19]Zarubin T, Han J: Activation and signaling of the p38 MAP kinase pathway. Cell Res 2005, 15:11-18.
• [20]Wang WZ, Guo X, Duan CH, et al.: Comparative analysis of gene expression profiles between the normal human cartilage and the one with endemic osteoarthritis. Osteoarthr Cartilage 2009, 17:83-90.
• [21]Guo X, Zuo H, Cao CX, et al.: Abnormal expression of Col X, PTHrP, TGF-β, bFGF, and VEGF in cartilage with Kashin-Beck disease. J Bone Min Metab 2006, 24:319-328.
• [22]Guo X: Diagnostic, clinical and radiological characteristics of Kashin-Beck disease in Shaanxi Province, PR China. Int Orthop 2001, 25:147-150.
• [23]Kenneth JL, Thomas DS: Analysis of relative gene expression data using Real-Time quantitative PCR and the 2–∆∆CT method. Methods 2001, 25:402-408.
• [24]Cao JL, Li SY, Shi ZL, et al.: Articular cartilage metabolism in patients with Kashin-Beck disease: an endemic osteoarthropathy in China. Osteoarthr Cartilage 2008, 16:680-688.
• [25]Wang SJ, Guo X, Zuo H, et al.: Chondrocyte apoptosis and expression of Bcl-2, Bax, Fas, and iNOS in articular cartilage in patients with Kashin-Beck disease. J Rheumatol 2006, 33:615-619.
• [26]Zhang BD, Guo X, Bai GL, et al.: The changes of nitric oxide, NO syntheses and Fas/APO-1 in serum among the patients with Kashin-Beck disease. Chin J Entomol 2006, 23:172-175.
• [27]Wei XQ, Zhang J, Cao JL, et al.: Culture rabbit chondrocytes with serum from children with Kashin- Beck disease. Chin J Endemiol 1990, 9:90-93.
• [28]Yan WQ, Yu L, Cunmaofu Z, et al.: Effect of serum of KBD patients on metabolism of proteoglycan in rabbit hypertrophic chondrocyte cultures. Chin J Endemiol 1994, 13:323-325.
• [29]Gupta S, Campbell D, Dérijard B, et al.: Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science 1995, 267:389-393.
• [30]Ip YT, Davis RJ: Signal transduction by the c-Jun N-terminal kinase (JNK)-from inflammation to development. Curr Opin Cell Biol 1998, 10:205-219.
• [31]Nakano H, Nakajima A, Sakon SK, et al.: Reative oxygen species mediate crosstalk between NF- κB and JNK. Cell Death Differ 2006, 13:730-737.
• [32]Hwang SG, Yu SS, Lee SW, et al.: Wnt-3a regulates chondrocyte differentiation via c-Jun/AP-1 pathway. FEBS Lett 2005, 579:4837-4842.
• [33]Arbogast S, Ferreiro A: Selenoproteins and protection against oxidative stress: selenoprotein N as a novel player at the crossroads of redox signaling and calcium homeostasis. Antioxid Redox Sign 2010, 12:893-904.
• [34]Bellinger FP, Raman AV, Reeves MA, et al.: Regulation and function of selenoproteins in human disease. Biochem J 2009, 422:11-22.
• [35]Pace JG: Effect of T-2 mycotoxin on rat liver mitochondria electron transport system. Toxicon 1983, 21:675-680.
• [36]Liu JT, Guo X, Ma WJ, et al.: Mitochondrial function is altered in articular chondrocytes of an endemic osteoarthritis, Kashin-Beck disease. Osteoarthr Cartilage 2010, 18:1218-1226.
• [37]Guan F, Li SY, Wang ZL, et al.: 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 2013, 33:157-166.
• [38]Han J, Guo X, Lei YX, et al.: Synthesis and characterization of selenium–chondroitin sulfate nanoparticles. Carbohyd Polym 2012, 90:122-126.