Chinese Journal of Tissue Engineering Research ›› 2015, Vol. 19 ›› Issue (18): 2807-2813.doi: 10.3969/j.issn.2095-4344.2015.18.004
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Ye Pei1, Li Jian-hua2, Xu Jin-huang3, Huang Sheng-hui1, Liu Gui-wang1, Zhang Wei-qiong3, Zheng Pei-zhong3, Huang Jian-rong1, 3
Received:
2015-03-16
Online:
2015-04-30
Published:
2015-04-30
Contact:
Huang Jian-rong, M.D., Associate professor, Master’s supervisor, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China; Department of Orthopedics, Zengcheng People’s Hospital, Guangzhou 511300, Guangdong Province, China
About author:
Ye Pei, Studying for master’s degree, Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
Supported by:
Science and Technology Foundation of Guangdong Province, No. 2010B031600184; Key Program of Science and Technology Bureau of Guangzhou, No. 11C31120789; the Natural Science Foundation of Guangdong Province, No. S2012010010629, S2013010013768
CLC Number:
Ye Pei, Li Jian-hua, Xu Jin-huang, Huang Sheng-hui, Liu Gui-wang, Zhang Wei-qiong, Zheng Pei-zhong, Huang Jian-rong. Triggering receptor expressed on myeloid cells 2 in synovial tissue of rheumatoid arthritis rats[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(18): 2807-2813.
2.1 实验动物数量分析 纳入25只SD大鼠,模型组15只SD大鼠成模10只,无脱落,最终共20只SD大鼠纳入结果分析。建模流程图见图1。 2.2 诱导性关节炎大鼠模型的鉴定结果 对照组大鼠在实验期间未发现四肢足爪红肿,无炎症表现。诱导性关节炎大鼠在初次免疫13 d后,开始出现关节炎体征,19-25 d病变最为严重,包括掌骨和趾骨关节、远端和近端指间关节都出现明显肿胀。免疫4周,大鼠关节炎仍明显,见图2A1-B1。初次免疫后不同时间点实验大鼠关节炎指数评分,见表2。病理切片苏木精-伊红染色显示:模型组大鼠有大量炎性细胞浸润及滑膜组织增生,骨、软骨破坏,关节融合强直,见图2A2-B2。综上表明诱导性关节炎大鼠模型建立成功。 2.3 TREM-2在大鼠膝关节滑膜中mRNA和蛋白的表达差异 初次免疫28 d后,RT-PCR结果显示:与对照组相比,模型组大鼠膝关节滑膜组织中TREM-2 mRNA和蛋白表达明显升高(P < 0.01),见图3A-C。 2.4 TREM-2在大鼠踝关节滑膜中的表达及定位差异 初次免疫28 d后,免疫组织化学染色结果显示:对照组TREM-2表达水平极低,诱导性关节炎大鼠模型的TREM-2阳性细胞明显增多(P < 0.01),多集中在滑膜衬里层及衬里下层滑膜细胞、浸润的炎性细胞以及部分血管内皮细胞,见图3D,E。 2.5 肿瘤坏死因子α、白细胞介素1β及白细胞介素10 mRNA在大鼠膝关节滑膜组织中的表达差异 初次免疫 28 d后,RT-PCR法检测结果显示:与对照组相比,模型组大鼠膝关节滑膜组织中肿瘤坏死因子α、白细胞介素1β mRNA表达明显升高(P < 0.05),而白细胞介素10 mRNA水平明显降低(P < 0.05),见图4。"
[1] Vivar N, Van Vollenhoven RF. Advances in the treatment of rheumatoid arthritis. F1000Prime Rep. 2014;6:31. [2] 莫选荣,罗心静.类风湿性关节炎发病机制的研究进展[J].医学临床研究,2007;(2):336-340. [3] Kasperkovitz PV, Timmer TC, Smeets TJ, et al. Fibroblast-like synoviocytes derived from patients with rheumatoid arthritis show the imprint of synovial tissue heterogeneity: evidence of a link between an increased myofibroblast-like phenotype and high-inflammation synovitis. Arthritis Rheum. 2005;52(2): 430-441. [4] 谢庆云,魏萌,张波,等.外周血炎性细胞因子与类风湿关节炎[J].中国组织工程研究,2012(42):7945-7950. [5] Bouchon A, Dietrich J, Colonna M. Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol. 2000;164(10):4991-4995. [6] Ito H, Hamerman JA. TREM-2, triggering receptor expressed on myeloid cell-2, negatively regulates TLR responses in dendritic cells. Eur J Immunol. 2012;42(1):176-185. [7] Gao X, Dong Y, Liu Z, et al. Silencing of triggering receptor expressed on myeloid cells-2 enhances the inflammatory responses of alveolar macrophages to lipopolysaccharide. Mol Med Rep. 2013;7(3):921-926. [8] Chen Q, Zhang K, Jin Y, et al. Triggering receptor expressed on myeloid cells-2 protects against polymicrobial sepsis by enhancing bacterial clearance. Am J Respir Crit Care Med. 2013;188(2):201-212. [9] Kleinberger G, Yamanishi Y, Suarez-Calvet M, et al. TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci Transl Med. 2014;6(243): 243r-286r. [10] Crotti TN, Dharmapatni AA, Alias E, et al. The immunoreceptor tyrosine-based activation motif (ITAM) -related factors are increased in synovial tissue and vasculature of rheumatoid arthritic joints. Arthritis Res Ther. 2012;14(6):R245. [11] Trentham DE, Townes AS, Kang AH. Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med. 1977; 146(3):857-868. [12] 陈欢雪,王晓非.间充质干细胞移植治疗4种风湿性疾病:10年资料分析[J].中国组织工程研究,2014,(14):2263-2268. [13] Kaur K, Kalra S, Kaushal S. Systematic review of tofacitinib: a new drug for the management of rheumatoid arthritis. Clin Ther. 2014;36(7):1074-1086. [14] Feldmann M, Brennan FM, Maini RN. Rheumatoid arthritis. Cell. 1996;85(3):307-310. [15] Noss EH, Brenner MB. The role and therapeutic implications of fibroblast-like synoviocytes in inflammation and cartilage erosion in rheumatoid arthritis. Immunol Rev. 2008;223: 252-270. [16] 杨慧君,钱玉中,杨继章,等.胶原性关节炎大鼠滑膜组织细胞因子基质金属蛋白酶3和组织金属蛋白酶抑制剂1表达的变化[J].中国组织工程研究与临床康复,2007(32):6402-6405. [17] McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7(6):429-442. [18] Pap T, Meinecke I, Muller-Ladner U, et al. Are fibroblasts involved in joint destruction? Ann Rheum Dis. 2005;64 Suppl 4:v52-v54. [19] Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010; 233(1):233-255. [20] Yoshida K, Hashimoto T, Sakai Y, et al. Involvement of the circadian rhythm and inflammatory cytokines in the pathogenesis of rheumatoid arthritis. J Immunol Res. 2014; 2014:282495. [21] 侯春凤,孙闵,李树杰,等.小干扰RNA对人类风湿关节炎患者滑膜细胞基因表达的影响[J].中国组织工程研究,2013,(46):8062- 8068. [22] 燕鹏.肿瘤坏死因子-α抑制剂(益赛普)治疗类风湿关节炎的meta分析[D].济南:山东大学,2008. [23] 刘彧,韩星海,孟济明.生物制剂在类风湿关节炎治疗中的应用[J].中华风湿病学杂志,2003(05):300-302. [24] Augello A, Tasso R, Negrini SM, et al. Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis. Arthritis Rheum. 2007;56(4):1175-1186. [25] Sharif O, Knapp S. From expression to signaling: roles of TREM-1 and TREM-2 in innate immunity and bacterial infection. Immunobiology. 2008;213(9-10):701-713. [26] N'Diaye EN, Branda CS, Branda SS, et al. TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria. J Cell Biol. 2009;184(2):215-223. [27] Rajagopalan P, Hibar DP, Thompson PM. TREM2 and neurodegenerative disease. N Engl J Med. 2013;369(16): 1565-1567. [28] Sun M, Zhu M, Chen K, et al. TREM-2 promotes host resistance against Pseudomonas aeruginosa infection by suppressing corneal inflammation via a PI3K/Akt signaling pathway. Invest Ophthalmol Vis Sci. 2013;54(5):3451-3462. [29] Turnbull IR, Gilfillan S, Cella M, et al. Cutting edge: TREM-2 attenuates macrophage activation. J Immunol. 2006;177(6): 3520-3524. [30] Ford J W, McVicar D W. TREM and TREM-like receptors in inflammation and disease. Curr Opin Immunol. 2009;21(1): 38-46. [31] Suchankova M, Bucova M, Tibenska E, et al. Triggering receptor expressed on myeloid cells-1 and 2 in bronchoalveolar lavage fluid in pulmonary sarcoidosis. Respirology. 2013;18(3):455-462. [32] Piccio L, Buonsanti C, Mariani M, et al. Blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis. Eur J Immunol. 2007;37(5):1290-1301. [33] Oh JH, Yang MJ, Heo JD, et al. Inflammatory response in rat lungs with recurrent exposure to welding fumes: a transcriptomic approach. Toxicol Ind Health. 2012;28(3): 203-215. [34] 秦涛.TREM-1、TREM-2在非酒精性脂肪性肝炎时肝组织表达的研究[D].太原:山西医科大学,2012. [35] 沈茜.TREM-2在非小细胞肺癌中的表达及意义[D].杭州:浙江大学,2009. [36] Paradowska-Gorycka A, Jurkowska M. Structure, expression pattern and biological activity of molecular complex TREM-2/DAP12. Hum Immunol. 2013;74(6):730-737. [37] Sun GY, Guan CX, Zhou Y, et al. Vasoactive intestinal peptide re-balances TREM-1/TREM-2 ratio in acute lung injury. Regul Pept. 2011;167(1):56-64. [38] Humphrey MB, Daws MR, Spusta SC, et al. TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. J Bone Miner Res. 2006;21(2): 237-245. [39] Colonna M, Turnbull I, Klesney-Tait J. The enigmatic function of TREM-2 in osteoclastogenesis. Adv Exp Med Biol. 2007;602:97-105. [40] Otero K, Shinohara M, Zhao H, et al. TREM2 and beta-catenin regulate bone homeostasis by controlling the rate of osteoclastogenesis. J Immunol. 2012;188(6): 2612-2621. [41] 李淑芬.TREM-2对小鼠成纤维细胞增殖与凋亡的影响及VIP的调控[D].长沙:中南大学,2012. [42] Park M, Yi JW, Kim EM, et al. Triggering receptor expressed on myeloid cells 2 (TREM2) promotes adipogenesis and diet-induced obesity. Diabetes. 2015;64(1):117-127. [43] Lis K, Kuzawińska O, Ba?kowiec-Iskra E. Tumor necrosis factor inhibitors - state of knowledge. Arch Med Sci. 2014; 10(6):1175-1185. [44] Wang Y, Wang S, Li Y, et al. Therapeutic effect of Cryptotanshinone on collagen-induced arthritis in rats via inhibiting nuclear factor kappa B signaling pathway. Transl Res. 2014. doi: 10.1016/j.trsl.2014.12.004. [45] Goedken ER, Argiriadi MA, Banach DL, et al. Tricyclic Covalent Inhibitors Selectively Target Jak3 through an Active Site Thiol. J Biol Chem. 2015;290(8):4573-4589. [46] Xu CP, Li X, Hu YJ, et al. Quantitative proteomics reveals ELP2 as a regulator to the inhibitory effect of TNF-α on osteoblast differentiation. J Proteomics. 2015;114:234-2346. [47] Meier FM, McInnes IB. Small-molecule therapeutics in rheumatoid arthritis: scientific rationale, efficacy and safety. Best Pract Res Clin Rheumatol. 2014;28(4):605-624. [48] Klein K, Kabala PA, Grabiec AM, et al. The bromodomain protein inhibitor I-BET151 suppresses expression of inflammatory genes and matrix degrading enzymes in rheumatoid arthritis synovial fibroblasts. Ann Rheum Dis. 2014. doi: 10.1136/annrheumdis-2014-205809. [49] Damento G, Kavoussi SC, Materin MA, et al. Clinical and histologic findings in patients with uveal melanomas after taking tumor necrosis factor-α inhibitors. Mayo Clin Proc. 2014;89(11):1481-1486. [50] Liu Q, Zhao J, Tan R, et al. Parthenolide inhibits pro-inflammatory cytokine production and exhibits protective effects on progression of collagen-induced arthritis in a rat model. Scand J Rheumatol. 2014:1-10. [51] Fuggle NR, Howe FA, Allen RL, et al. New insights into the impact of neuro-inflammation in rheumatoid arthritis. Front Neurosci. 2014;8:357. [52] Zanin-Zhorov A, Weiss JM, Nyuydzefe MS, et al. Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism. Proc Natl Acad Sci U S A. 2014;111(47):16814-16819. [53] Wadström H, Eriksson JK, Neovius M, et al. How good is the coverage and how accurate are exposure data in the Swedish Biologics Register (ARTIS)? Scand J Rheumatol. 2015;44(1): 22-28. [54] Zheng Y, Hou J, Peng L, et al. The pro-apoptotic and pro-inflammatory effects of calprotectin on human periodontal ligament cells. PLoS One. 2014;9(10):e110421 |
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