期刊论文详细信息
Journal of Foot and Ankle Research
IL-17 cytokines in bone healing of diabetic Charcot arthropathy patients: a prospective 2 year follow-up study
Jean Cassuto4  Jan Göthlin5  Ylva Aurell5  Jesper Fowelin1  Susanne Asteberg3  Martin Ålund3  Agnetha Folestad2 
[1] Diabetes Care Unit, Department of Medicine, Frölunda Specialist Hospital, Västra Frölunda, Göteborg, Sweden;Department of Orthopaedics, CapioLundby Hospital, Göteborg, Sweden;Department of Orthopaedics, Sahlgrenska University Hospital, Mölndal, Sweden;Orthopaedic Research Unit, Sahlgrenska University Hospital, Staben, Hus U1, 431 80 Mölndal, Sweden, Göteborg University, Göteborg, Sweden;Department of Radiology, Sahlgrenska University Hospital, Mölndal, Sweden
关键词: Diabetes;    Interleukin-17;    Offloading;    Bone healing;    Charcot arthropathy;   
Others  :  1224860
DOI  :  10.1186/s13047-015-0096-3
 received in 2015-03-03, accepted in 2015-08-04,  发布年份 2015
PDF
【 摘 要 】

Background

Little is currently known of the pathophysiological mechanisms triggering Charcot arthropathy and regulating its recovery although foot trauma has been proposed as a major initiating factor by activation of proinflammatory cytokines leading to increased osteoclastogenic activity and progressive bone destruction. Several members of the IL-17 family of proinflammatory cytokines have been shown to play a key role in the pathogenesis of inflammatory conditions affecting bone and joints but none has previously been studied in Charcot foot patients. The aim of this study was to investigate the role of IL-17A, IL-17E and IL-17F in patients presenting with Charcot foot.

Methods

Twenty-six consecutive Charcot patients were monitored during 2 years by repeated foot radiographs, MRI and circulating levels of IL-17A, IL-17E and IL-17F. Analysis of cytokines was done by ultra-sensitive chemiluminescence technique and data were analyzed by one-way repeated measures ANOVA. Neuropathic diabetic patients (n = 20) and healthy subjects (n = 20) served as controls.

Results

Plasma IL-17A and IL-17E in weight-bearing Charcot patients at diagnosis were at the level of diabetic controls, whereas IL-17F was significantly lower than diabetic controls. A significant increase in IL-17A and IL-17E reaching a peak 2–4 months after inclusion and start of offloading treatment in Charcot patients was followed by a gradual decrease to the level of diabetic controls at 2 years postinclusion. In contrast, IL-17F increased gradually from inclusion to a level not significantly different from diabetic controls after 2 years.

Conclusions

Charcot patients display a significant elevation of all three IL-17 cytokines during the follow-up period relative values at diagnosis and values in control patients supporting a role in the bone repair and remodeling activity during the recovery phase. The rapid increase of IL-17A and IL-17E shortly after initiating off-loading treatment could suggest this to be a response to immobilization and stabilization of the diseased foot.

【 授权许可】

   
2015 Folestad et al.

【 预 览 】
附件列表
Files Size Format View
20150914093558423.pdf 728KB PDF download
Fig. 3. 39KB Image download
Fig. 2. 34KB Image download
Fig. 1. 35KB Image download
【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

【 参考文献 】
  • [1]Rogers LC, Frykberg RG. The charcot foot. Med Clin North Am. 2013; 97:847-56.
  • [2]Jeffcoate WJ. Abnormalities of vasomotor regulation in the pathogenesis of the acute charcot foot of diabetes mellitus. Int J Low Extrem Wounds. 2005; 4:133-7.
  • [3]Jones CW, Agolley D, Burns K, Gupta S, Horsley M. Charcot arthropathy presenting with primary bone resorption. Foot. 2012; 22:258-63.
  • [4]Jeffcoate WJ, Game F, Cavanagh PR. The role of proinflammatory cytokines in the cause of neuropathic osteoarthropathy (acute Charcot foot) in diabetes. Lancet. 2005; 366:2058-61.
  • [5]Folestad A, Alund M, Asteberg S, Fowelin J, Aurell Y, Gothlin J et al.. Role of Wnt/beta-catenin and RANKL/OPG in bone healing of diabetic Charcot arthropathy patients. Acta Orthop. 2015; 4:1-11.
  • [6]Charles JF, Nakamura MC. Bone and the innate immune system. Curr Osteoporos Rep. 2014; 12:1-8.
  • [7]Bluml S, Redlich K, Smolen JS. Mechanisms of tissue damage in arthritis. Semin Immunopathol. 2014; 36:531-40.
  • [8]Brown KD, Claudio E, Siebenlist U. The roles of the classical and alternative nuclear factor-kappaB pathways: potential implications for autoimmunity and rheumatoid arthritis. Arthritis Res Ther. 2008; 10:212. BioMed Central Full Text
  • [9]Witowski J, Ksiazek K, Jorres A. Interleukin-17: a mediator of inflammatory responses. Cell Mol Life Sci. 2004; 61:567-79.
  • [10]Kotake S, Yago T, Kawamoto M, Nanke Y. Role of osteoclasts and interleukin-17 in the pathogenesis of rheumatoid arthritis: crucial ‘human osteoclastology’. J Bone Miner Metab. 2012; 30:125-35.
  • [11]Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L et al.. Regulation of inflammatory responses by IL-17F. J Exp Med. 2008; 205:1063-75.
  • [12]Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y et al.. Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity. 2009; 30:108-19.
  • [13]von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP et al.. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies. Int J Surg. 2014; 12:1495-9.
  • [14]Weinstein S. Fifty years of somatosensory research: from the Semmes-Weinstein monofilaments to the Weinstein Enhanced Sensory Test. J Hand Ther. 1993; 6:11-22.
  • [15]Samuelsson P, Blohme G, Fowelin J, Eriksson JW. A new non-invasive method using pulse oximetry for the assessment of arterial toe pressure. Clin Physiol. 1996; 16:463-7.
  • [16]Fu Q, Zhu J, Van Eyk JE. Comparison of multiplex immunoassay platforms. Clin Chem. 2010; 56:314-8.
  • [17]Papanas N, Maltezos E. Etiology, pathophysiology and classifications of the diabetic Charcot foot. Diabet Foot Ankle. 2013;4:20872.
  • [18]Sella EJ, Barrette C. Staging of Charcot neuroarthropathy along the medial column of the foot in the diabetic patient. J Foot Ankle Surg. 1999; 38:34-40.
  • [19]Chen H, Wen F, Zhang X, Su SB. Expression of T-helper-associated cytokines in patients with type 2 diabetes mellitus with retinopathy. Mol Vis. 2012; 18:219-26.
  • [20]Afzal N, Zaman S, Asghar A, Javed K, Shahzad F, Zafar A et al.. Negative association of serum IL-6 and IL-17 with type-II diabetes retinopathy. Iran J Immunol. 2014; 11:40-8.
  • [21]Roohi A, Tabrizi M, Abbasi F, Ataie-Jafari A, Nikbin B, Larijani B et al.. Serum IL-17, IL-23, and TGF- beta Levels in Type 1 and Type 2 Diabetic Patients and Age—Matched Healthy Controls. Biomed Res Int. 2014; 2014:718946.
  • [22]Arababadi MK, Nosratabadi R, Hassanshahi G, Yaghini N, Pooladvand V, Shamsizadeh A et al.. Nephropathic complication of type-2 diabetes is following pattern of autoimmune diseases? Diabetes Res Clin Pract. 2010; 87:33-7.
  • [23]Kumar NP, George PJ, Kumaran P, Dolla CK, Nutman TB, Babu S. Diminished Systemic and Antigen-Specific Type 1, Type 17, and Other Proinflammatory Cytokines in Diabetic and Prediabetic Individuals With Latent Mycobacterium tuberculosis Infection. J Infect Dis. 2014; 210:1670-8.
  • [24]Schett G. Effects of inflammatory and anti-inflammatory cytokines on the bone. Eur J Clin Invest. 2011; 41:1361-6.
  • [25]Lee Y. The role of interleukin-17 in bone metabolism and inflammatory skeletal diseases. BMB Rep. 2013; 46:479-83.
  • [26]Benedetti G, Miossec P. Interleukin 17 contributes to the chronicity of inflammatory diseases such as rheumatoid arthritis. Eur J Immunol. 2014;44:339–47.
  • [27]Moseley TA, Haudenschild DR, Rose L, Reddi AH. Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev. 2003; 14:155-74.
  • [28]Bedoya SK, Lam B, Lau K, Larkin J. Th17 Cells in Immunity and Autoimmunity. Clin Dev Immunol. 2013; 2013:986789.
  • [29]Kaiwen W, Zhaoliang S, Yinxia Z, Siamak SS, Zhijun J, Yuan X et al.. Changes and significance of IL-25 in chicken collagen II-induced experimental arthritis (CIA). Rheumatol Int. 2012; 32:2331-8.
  • [30]Folestad A ÅM, Fowelin J, Asteberg S, Aurell Y, Göthlin J, Cassuto J. Role of Wnt/β-catenin and RANKL/OPG in bone healing of diabetic Charcot arthropathy patients. A prospective study in 24 patients followed during 2 years. Acta Orthopaedica. Eur J Immunol. 2014;44:339–47.
  • [31]Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky MS, Dwyer D et al.. Dickkopf-1 is a master regulator of joint remodeling. Nat Med. 2007; 13:156-63.
  • [32]Sen M, Reifert J, Lauterbach K, Wolf V, Rubin JS, Corr M et al.. Regulation of fibronectin and metalloproteinase expression by Wnt signaling in rheumatoid arthritis synoviocytes. Arthritis Rheum. 2002; 46:2867-77.
  • [33]Caetano-Lopes J, Lopes A, Rodrigues A, Fernandes D, Perpetuo IP, Monjardino T et al.. Upregulation of inflammatory genes and downregulation of sclerostin gene expression are key elements in the early phase of fragility fracture healing. PLoS One. 2011; 6:e16947.
  • [34]Daoussis D, Andonopoulos AP, Liossis SN. Wnt pathway and IL-17: novel regulators of joint remodeling in rheumatic diseases. Looking beyond the RANK-RANKL-OPG axis. Semin Arthritis Rheum. 2010; 39:369-83.
  • [35]Daoussis D, Andonopoulos AP. The emerging role of Dickkopf-1 in bone biology: is it the main switch controlling bone and joint remodeling? Semin Arthritis Rheum. 2011; 41:170-7.
  • [36]Gouveri E, Papanas N. Charcot osteoarthropathy in diabetes: A brief review with an emphasis on clinical practice. World J Diabetes. 2011; 2:59-65.
  • [37]Nam D, Mau E, Wang Y, Wright D, Silkstone D, Whetstone H et al.. T-lymphocytes enable osteoblast maturation via IL-17F during the early phase of fracture repair. PLoS One. 2012; 7:e40044.
  • [38]Einhorn TA, Gerstenfeld LC. Fracture healing: mechanisms and interventions. Nat Rev Rheumatol. 2015; 11:45-54.
  • [39]Kim JH, Liu X, Wang J, Chen X, Zhang H, Kim SH et al.. Wnt signaling in bone formation and its therapeutic potential for bone diseases. Ther Adv Musculoskelet Dis. 2013; 5:13-31.
  文献评价指标  
  下载次数:8次 浏览次数:11次