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首页> 外文期刊>Orthopaedic Journal of Sports Medicine >Gene expression in meniscus tears at the time of arthroscopic partial meniscectomy predicts osteoarthritis progression
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Gene expression in meniscus tears at the time of arthroscopic partial meniscectomy predicts osteoarthritis progression

机译：关节镜分数末末末切除术时弯月面眼泪的基因表达预测骨关节炎进展

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Objectives: While meniscus tears are associated with an increased risk of developing knee osteoarthritis (OA), it is not possible to predict which patients are at the highest risk for developing OA. Gene signature in meniscus resected at the time of arthroscopic partial meniscectomy may provide insight into an individual’s risk of OA progression. The purpose of this study is to test the hypothesis that gene signatures at the time of arthroscopic partial meniscectomy predict radiographic progression of OA. Methods: Meniscus fragments were collected from 40 patients at the time of clinically indicated isolated arthroscopic partial medial meniscectomy. Gene expression was assessed by quantitative real-time PCR using a panel of 28 candidate genes with known roles in cartilage homeostasis, OA, extracellular-matrix degradation and obesity. Radiographs obtained prior to surgery and at final follow-up were graded by a musculoskeletal radiologist. The association of meniscus gene expression at the time of surgery with progression of radiographic OA was determined. Results: Gene expression in meniscus resected at arthroscopic partial medial meniscectomy and radiographic data at baseline and mean follow-up of 6.2 ± 1.3 years were available for 31 patients (77.5%). The cohort consisted of 45.2% females with a mean age of 48.5 ± 9.2 years and mean body mass index of 28.1 ± 5.1 kg/m2. Gene expression was associated with radiographic progression of OA (Table 1). Patients without OA progression had significantly higher expression of seven genes, namely MMP9 (5.1-fold, P=0.002), IL8 (2.9-fold, P=0.016), CCL3 (3.7-fold, P=0.032), CCL3L1 (4.5-fold, P=0.008), CXCL6 (6.2-fold, P=0.010), LEP (5.2-fold, P=0.004) and RETN (46-fold, P=0.008). Patients with progression showed very low expression of these genes (Figure 1). When segregating patients based on severity of OA progression, there was significantly increased expression of three genes (MMP9, CXCL6, LEP) among patients without any radiographic OA progression. There was an increased expression of CXCL6 (9.5-fold, P=0.042), LEP (4.3-fold, P=0.047) and MMP9 (5.0-fold, P=0.023) among those without any radiographic OA progression compared to those with rapid progression in the medial compartment. There was also an increased expression of MMP9 among patients without progression compared to those with progression in the lateral and/or patellofemoral compartments (7.2-fold, P=0.038). Conclusions: Our findings suggest that gene expression in the meniscus at the time of arthroscopic partial meniscectomy is associated with the risk for OA progression. Elevated expression of the aforementioned genes in non-progressors may reflect a potentially chondroprotective response. Further studies including additional genes, larger cohorts and extended follow-up are warranted to better characterize this association. Ultimately, this line of investigation could facilitate the development of more sensitive methods to determine the risk for OA progression among patients with meniscal injury and approaches to delay or prevent OA in this population.
机译：目的：虽然弯月面眼泪与发育膝关节骨关节炎的风险增加（OA）的风险增加，但无法预测哪些患者处于开发OA的最高风险。在关节镜的部分夜总会切除术时切除的半月板中的基因签名可能会对个人的OA进步风险提供洞察力。本研究的目的是测试关节镜分数预测OA的关节镜分数预测基因签名的假设。方法：在临床上显示分离的关节镜分离的部分内侧半月切除术的40例患者中收集了弯月面片段。通过使用28个候选基因的定量实时PCR评估基因表达，其中包含在软骨稳态，OA，细胞外 - 基质降解和肥胖症中具有已知作用的。在手术之前获得的射线照相和最终随访的肌肉骨骼放射科医师分级。确定了射线照相OA进展手术时弯月面基因表达的关联。结果：在31名患者中可获得在基线的关节镜部分内侧膜骨切除术和射线照相数据的半月板中切割的基因表达，31例患者可获得6.2±1.3岁（77.5％）。队列由45.2％的女性组成，平均年龄为48.5±9.2岁，平均体重指数为28.1±5.1 kg / m 2。基因表达与OA的放射线进展相关（表1）。没有OA进展的患者具有7个基因的表达显着高，即MMP9（5.1倍，P = 0.002），IL8（2.9倍，P = 0.016），CCL3（3.7倍，P = 0.032），CCL3L1（4.5-折叠，p = 0.008），CXCL6（6.2倍，P = 0.010），LEP（5.2倍，P = 0.004）和RETN（46倍，P = 0.008）。进展的患者表现出这些基因的表达非常低（图1）。当基于OA进展的严重程度进行分离患者时，没有任何放射线摄影OA进展的患者的三种基因表达（MMP9，CXCL6，LEP）显着增加。在没有任何射线照相OA进展的情况下，CXCL6（9.5倍，P = 0.042），LEP（4.3倍，P = 0.047），LEP（4.3倍，P = 0.047）和MMP9（5.0倍，P = 0.023）的表达增加内侧舱的进展。与横向和/或髌椎间室中的进展相比，没有进展的患者中MMP9的表达增加了（7.2倍，P = 0.038）。结论：我们的研究结果表明，关节镜分数末末期切除术时弯月面中的基因表达与OA进展的风险有关。在非进化体中上述基因的升高表达可能反映出可能的软骨制性反应。需要进一步的研究，包括额外的基因，较大的群组和延长的随访，以更好地表征本协会。最终，这种调查系列可以促进开发更敏感的方法，以确定半月板伤害患者患者的OA进展的风险，以及在本人中延迟或预防OA的途径。

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