Molecular Analysis of Age and Sex-Related Gene Expression in Meniscal Tears with and without a Concomitant Anterior Cruciate Ligament Tear
Molecular Analysis of Age and Sex-Related Gene Expression in Meniscal Tears with and without a Concomitant Anterior Cruciate Ligament Tear
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DOI：
10.2106/jbjs.k.00919
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发表时间：
2012-03-07
影响因子：
5.3
通讯作者：
Sandell, Linda J.
中科院分区：
文献类型：
--
作者：
Brophy, Robert H.;Rai, Muhammad Farooq;Sandell, Linda J.
背景：半月板在膝关节中起着至关重要的作用，有助于负荷传递、减震和关节稳定。人们对半月板撕裂的基因表达知之甚少，特别是与损伤类型和患者年龄和性别的关系。这项研究的目的是验证半月板撕裂中基因表达随患者年龄和性别以及前交叉韧带(ACL)是否也被撕裂而变化的假设。方法：收集28例半月板撕裂患者的半月板组织，这些患者在临床表现为半月板部分切除时，半月板撕裂或半月板撕裂合并前交叉韧带撕裂。用实时定量聚合酶链式反应检测骨性关节炎的分子标志物，包括促炎细胞因子(IL-1α、IL-1β、IL-6和肿瘤坏死因子-α[TNF-α])、趋化因子(IL-8、CCL3、CCL3L1、CXCL1、CXCL3、CXCL6和CCL20)、聚集素酶(ADAMTS-4[一种具有血栓反应蛋白4型基序的去整合素和金属蛋白酶]和ADAMTS-5)、基质金属蛋白酶(基质金属蛋白-1、基质金属蛋白酶-3、基质金属蛋白酶-9和基质金属蛋白酶-13)、转录因子(核因子-kappa B2、核因子-kappa B2)和聚集酶(ADAMTS-4和ADAMTS-5)。结果：IL-1β(p=0.02)、ADAMTS-5(p=0.001)、MMP1(p=0.007)、MMP一9(p=0.002)、MMP一13(p=0.01)、40岁以下半月板撕裂患者血清中核因子-kappaB2水平显著高于40岁以上患者(p=0.01)。同样，ADAMTS-4(p=0.002)、ADAMTS-5(p=0.02)、MMP1(p=0.02)和MMP13(p=0.0002)在40岁以下的半月板撕裂和前交叉韧带撕裂患者中的表达均高于40岁以上的患者。在半月板撕裂和前交叉韧带撕裂患者中，IL-1β(p=0.01)、肿瘤坏死因子α(p=0.02)、基质金属蛋白酶-13(p=0.004)、CCl_3(p=0.03)和CCL_3L1(p=0.03)的表达显著高于半月板撕裂组，而aggrecan(p=0.03)的表达低于单独半月板撕裂组。基因表达的唯一性别差异是所有年龄段的合并损伤的女性患者中CCL3L1水平较高(p<；0.05)。结论和临床相关性：这些发现表明，在患者年龄和性别的基础上，膝关节对半月板撕裂的反应存在临床相关的差异。关节炎相关标记物的表达水平升高表明40岁以下患者的分解代谢反应增强。半月板撕裂和前交叉韧带撕裂患者中分解代谢标志物的高表达表明这种联合损伤模式更有可能导致骨关节炎的发展。半月板组织的分解代谢活性可预测半月板部分切除后有骨关节炎进展风险的患者。
Background: The meniscus plays critical roles in the knee, contributing to load transmission, shock absorption, and joint stability. Little is known about gene expression in meniscal tears, particularly in relation to injury pattern and patient age and sex. The purpose of this study was to test the hypothesis that gene expression in meniscal tears varies depending on patient age and sex and whether the anterior cruciate ligament (ACL) is also torn.Methods: Meniscal tissue from twenty-eight patients with an isolated meniscal tear or a meniscal tear with a concomitant ACL tear was collected at the time of clinically indicated partial meniscectomy. Messenger RNA (mRNA) expression was examined by quantitative real-time polymerase chain reaction for molecular markers of osteoarthritis including proinflammatory cytokines (interleukin [IL]-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor-alpha [TNF alpha]), chemokines (IL-8, CCL3, CCL3L1, CXCL1, CXCL3, CXCL6, and CCL20), aggrecanases (ADAMTS-4 [a disintegrin and metalloproteinase with thrombospondin type-4 motifs] and ADAMTS-5), matrix metalloproteinases (MMP-1, MMP-3, MMP-9, and MMP-13), transcription factors (NF kappa B2 [nuclear factor kappa B2], NF kappa BIA [NF-kappa B inhibitor alpha], and I kappa BA [inhibitor of kappa B alpha]), and matrix components (bone morphogenetic protein [BMP]-2, type-I collagen alpha 1 [Col1a1], Col2a1, and aggrecan).Results: Expression of IL-1 beta (p = 0.02), ADAMTS-5 (p = 0.001), MMP-1 (p = 0.007), MMP-9 (p = 0.002), MMP-13 (p = 0.01), and NF kappa B2 (p = 0.01) was significantly higher in patients with a meniscal tear who were under the age of forty years than it was in those over the age of forty years. Similarly, the expression of ADAMTS-4 (p = 0.002), ADAMTS-5 (p = 0.02), MMP-1 (p = 0.02), and MMP-13 (p = 0.0002) was higher in patients with a meniscal tear and an ACL tear who were under the age of forty years than it was in those over forty years. In patients with a meniscal tear and an ACL tear, the expression of IL-1 beta (p = 0.01), TNF alpha (p = 0.02), MMP-13 (p = 0.004), CCL3 (p = 0.03), and CCL3L1 (p = 0.03) was significantly higher, while that of aggrecan (p = 0.03) was lower, than that in patients with a meniscal tear alone. The only sex-based difference in gene expression was higher levels of CCL3L1 in female patients (p < 0.05) of all ages with combined injuries.Conclusions and Clinical Relevance: These findings suggest clinically relevant differences in the response of the knee to meniscal tears on the basis of patient age and sex. Elevated expression levels of arthritis-related markers indicate an increased catabolic response in patients under forty years old. Higher expression of catabolic markers in patients with meniscal and ACL tears suggests this combined injury pattern is more likely to lead to the development of osteoarthritis. Catabolic activity in meniscal tissue may predict patients who are at risk for progression of osteoarthritis following partial meniscectomy.