腰痛是骨科最常见症状之一,终板异常和椎间盘退变可能是椎间盘源性腰痛的病因.研究认为,退变腰椎终板与肿瘤坏死因子(TNF)-α的表达相关,TNF-α的高表达是产生疼痛的重要因素.作为能加速椎间盘退变的炎性因子,TNF-α在椎间盘退变过程中与其他基因产物有复杂的相互作用关系,目前已成为研究热点.作者就近几年国内外关于TNF-α与椎间盘退变关系的研究作一综述,进一步阐明TNF-α在椎间盘退变中的作用.

[1] MOONEY V.Presidential address.International Society for the Study of the Lumbar Spine.Dallas, 1986.Where is the pain coming from？[J].Spine (Phila Pa 1976),1987,12(8):754-759.
[2] 廖家新,王宸,吴小涛,等.退变腰椎终板MRI表现与其TNF-α的表达及临床疗效的相关性研究[J].现代医学,2008,36(3):201-203.
[3] WEILER C,NERLICH A G,BACHMEIER B E,et al.Expression and distribution of tumor necrosis factor alpha in human lumbar intervertebral discs:a study in surgical specimen and autopsy controls[J].Spine (Phila Pa 1976),2005,30(1):44-53;discussion 54.
[4] 闫军伟,李爱国,陈鸿辉.炎性细胞因子在椎间盘退变中的研究进展[J].中国矫形外科杂志,2012,20(24):2268-2271.
[5] 李茂.细胞因子在椎间盘退变中作用的研究进展[J].中国矫形外科杂志,2012,20(21):1960-1962.
[6] HIYAMA A,YOKOYAMA K,NUKAGA T,et al.A complex interaction between Wnt signaling and TNF-alpha in nucleus pulposus cells[J].Arthritis Res Ther,2013,15(6):R189.
[7] HOLM S,MACKIEWICZ Z,HOLM A K,et al.Pro-inflammatory,pleiotropic,and anti-inflammatory TNF-alpha,IL-6,and IL-10 in experimental porcine intervertebral disk degeneration[J].Vet Pathol, 2009,46(6):1292-300.
[8] Le MAITRE C L,HOYLAND J A,FREEMONT A J.Catabolic cytokine expression in degenerate and herniated human intervertebral discs:IL-1beta and TNFalpha expression profile[J].Arthritis Res Ther,2007,9(4):R77.
[9] BACHMEIER B E,NERLICH A G,WEILER C,et al.Analysis of tissue distribution of TNF-alpha,TNF-alpha-receptors,and the activating TNF-alpha-converting enzyme suggests activation of the TNF-alpha system in the aging intervertebral disc[J].Ann N Y Acad Sci,2007,1096:44-54.
[10] YOU C,ZHU K,LIU X,et al.Tumor necrosis factor-alpha-dependent infiltration of macrophages into the dorsal root ganglion in a rat disc herniation model[J].Spine (Phila Pa 1976),2013,38(23):2003-2007.
[11] KATO T,HARO H,KOMORI H,et al.Sequential dynamics of inflammatory cytokine,angiogenesis inducing factor and matrix degrading enzymes during spontaneous resorption of the herniated disc[J].J Orthop Res,2004,22(4):895-900.
[12] MAVROGONATOU E,ANGELOPOULOU M T,KLETSAS D.The catabolic effect of TNF α on bovine nucleus pulposus intervertebral disc cells and the restraining role of glucosamine sulfate in the TNF α-mediated up-regulation of MMP-3[J].J Orthop Res,2014,32(12):1701-1707.
[13] HARO H,CRAWFORD H C,FINGLETON B,et al.Matrix metalloproteinase-3-dependent generation of a macrophage chemoattractant in a model of herniated disc resorption[J].J Clin Invest,2000,105(2):133-141.
[14] HARO H,CRAWFORD H C,FINGLETON B,et al.Matrix metalloproteinase-7-dependent release of tumor necrosis factor-alpha in a model of herniated disc resorption[J].J Clin Invest,2000,105(2):143-150.
[15] ABE Y,AKEDA K,AN H S,et al.Proinflammatory cytokines stimulate the expression of nerve growth factor by human intervertebral disc cells[J].Spine (Phila Pa 1976),2007,32(6):635-642.
[16] MULLEMAN D,MAMMOU S,GRIFFOUL I,et al.Pathophysiology of disk-related sciatica.I.—Evidence supporting a chemical component[J].Joint Bone Spine,2006,73(2):151-158.
[17] WANG X,WANG H,YANG H,et al.Tumor necrosis factor-alpha-and interleukin-1beta-dependent matrix metalloproteinase-3 expression in nucleus pulposus cells requires cooperative signaling via syndecan 4 and mitogen-activated protein kinase-NF-kappaB axis:implications in inflammatory disc disease[J].Am J Pathol,2014,184(9):2560-2572.
[18] MILLWARD-SADLER S J,COSTELLO P W,FREEMONT A J,et al.Regulation of catabolic gene expression in normal and degenerate human intervertebral disc cells:implications for the pathogenesis of intervertebral disc degeneration[J].Arthritis Res Ther,2009,11(3):R65.
[19] SEGUIN C A,PILLIAR R M,ROUGHLEY P J,et al.Tumor necrosis factor-alpha modulates matrix production and catabolism in nucleus pulposus tissue[J].Spine (Phila Pa 1976),2005,30(17):1940-1948.
[20] SEGUIN C A,BOJARSKI M,PILLIAR R M,et al.Differential regulation of matrix degrading enzymes in a TNF alpha-induced model of nucleus pulposus tissue degeneration[J].Matrix Biol,2006,25(7):409-418.
[21] CHEN S,HUANG Y,ZHOU Z J,et al.Upregulation of tumor necrosis factor alpha and ADAMTS-5,but not ADAMTS-4,in human intervertebral cartilage endplate with modic changes[J].Spine (Phila Pa 1976),2014,39(14):E817-825.
[22] LIU F L,LIN L H,SYTWU H K,et al.GDF-5 is suppressed by IL-1beta and enhances TGF-beta3-mediated chondrogenic differentiation in human rheumatoid fibroblast-like synoviocytes[J].Exp Mol Pathol,2010,88(1):163-170.
[23] BRAMLAGE C P,KAPS C,UNGETHUM U,et al.Modulatory effects of inflammation and therapy on GDF-5 expression in rheumatoid arthritis synovium[J].Scand J Rheumatol,2008,37(6):401-409.
[24] GRUBER H E,HOELSCHER G L,INGRAM J A,et al.Growth and differentiation factor-5 (GDF-5) in the human intervertebral annulus cells and its modulation by IL-1ss and TNF-alpha in vitro[J].Exp Mol Pathol,2014,96(2):225-229.
[25] OHBA T,HARO H,ANDO T,et al.TNF-alpha-induced NF-kappaB signaling reverses age-related declines in VEGF induction and angiogenic activity in intervertebral disc tissues[J].J Orthop Res,2009,27(2):229-235.
[26] HARO H,KATO T,KOMORI H,et al.Vascular endothelial growth factor (VEGF)-induced angiogenesis in herniated disc resorption[J].J Orthop Res,2002,20(3):409-415.
[27] OHBA T,HARO H,ANDO T,et al.TNF-alpha-induced NF-kappaB signaling reverses age-related declines in VEGF induction and angiogenic activity in intervertebral disc tissues[J].J Orthop Res,2009,27(2):229-235.
[28] GABR M A,JING L,HELBLING A R,et al.Interleukin-17 synergizes with IFN γ or TNF α to promote inflammatory mediator release and intercellular adhesion molecule-1 (ICAM-1) expression in human intervertebral disc cells[J].J Orthop Res,2011,29(1):1-7.
[29] 周卫华,刘卓拉,王旭.血清IL-1β、TNF-α水平与急性肺血栓栓塞症和骨折的关系[J].东南大学学报:医学版,2006,25(4):275-277.
[30] KIM H J,YEOM J S,KOH Y G,et al.Anti-inflammatory effect of platelet-rich plasma on nucleus pulposus cells with response of TNF-alpha and IL-1[J].J Orthop Res,2014,32(4):551-556.
[31] BRANDT J,HAIBEL H,REDDIG J,et al.Successful short term treatment of severe undifferentiated spondyloarthropathy with the anti-tumor necrosis factor-alpha monoclonal antibody infliximab[J].J Rheumatol,2002,29(1):118-122.
[32] FUJITA K,ANDO T,OHBA T,et al.Age-related expression of MCP-1 and MMP-3 in mouse intervertebral disc in relation to TWEAK and TNF-alpha stimulation[J].J Orthop Res,2012,30(4):599-605.
[33] Le MAITRE C L,FREEMONT A J,HOYLAND J A.The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration[J].Arthritis Res Ther,2005,7(4):R732-745.
[34] STUDER R K,VO N,SOWA G,et al.Human nucleus pulposus cells react to IL-6:independent actions and amplification of response to IL-1 and TNF-alpha[J].Spine (Phila Pa 1976),2011,36(8):593-599.
[35] KIM H J,YEOM J S,KOH Y G,et al.Anti-inflammatory effect of platelet-rich plasma on nucleus pulposus cells with response of TNF-alpha and IL-1[J].J Orthop Res,2014,32(4):551-556.
[36] 范孟坡,王宸.椎间盘退变病因研究和治疗的最新进展[J].现代医学,2007,35(5):415-417.