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创伤性和退行性半月板撕裂具有不同的基因表达特征。

Traumatic and Degenerative Meniscus Tears Have Different Gene Expression Signatures.

作者信息

Brophy Robert H, Sandell Linda J, Rai Muhammad Farooq

机构信息

Department of Orthopaedic Surgery, Washington University School of Medicine, St Louis, Missouri, USA.

Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri, USA.

出版信息

Am J Sports Med. 2017 Jan;45(1):114-120. doi: 10.1177/0363546516664889. Epub 2016 Oct 1.

Abstract

BACKGROUND

Meniscus tears are classified as traumatic or degenerative based on the tear pattern. There is little evidence demonstrating biological differences between the 2 tear types.

HYPOTHESIS

Gene expression signatures in the injured meniscus are different between traumatic (vertical) and degenerative (complex, horizontal, or flap) tears.

STUDY DESIGN

Controlled laboratory study.

METHODS

Samples of the torn meniscus from the white-white zone were removed at the time of clinically indicated partial meniscectomy from 48 patients (37 with degenerative tears and 11 with traumatic tears). mRNA expression in the injured menisci was measured by quantitative real-time polymerase chain reaction for selected molecular markers of osteoarthritis, inflammation, and cartilage homeostasis (eg, cytokines/chemokines, aggrecanases/metalloproteinases, transcription factors, cartilage matrix genes, and adipokines). The tear pattern (traumatic or degenerative) and location (medial or lateral) were recorded for each patient. Gene expression differences between degenerative and traumatic tears were computed after adjusting for patients' age, sex, and body mass index and for location of the resected meniscus (medial/lateral).

RESULTS

Gene expression in meniscus tears varied by pattern. Chemokines ( IL8 [ P < .001] and CXCL6 [ P < .001]) and matrix metalloproteinases ( MMP1 [ P = .011] and MMP3 [ P = .016]) were expressed at a significantly higher level in traumatic tears compared with degenerative tears. In contrast, COL1A1 was expressed at a lower level in traumatic tears compared with degenerative tears ( P = .058). None of the genes tested demonstrated significant differences between medial and lateral meniscus tears.

CONCLUSION

Traumatic meniscus tears overall exhibited a higher inflammatory/catabolic response as evidenced by higher levels of chemokine and matrix metalloproteinase expression than degenerative tears. These findings suggest that there is a (molecular) biological distinction between traumatic and degenerative tears.

CLINICAL RELEVANCE

The catabolic/inflammatory differences between traumatic and degenerative tears may be relevant to treatment decisions regarding the meniscus as well as advance our understanding of how meniscus tears relate to the development of knee osteoarthritis.

摘要

背景

根据撕裂模式,半月板撕裂可分为创伤性或退变性。几乎没有证据表明这两种撕裂类型之间存在生物学差异。

假设

创伤性(垂直)和退变性(复杂、水平或瓣状)撕裂的损伤半月板中的基因表达特征不同。

研究设计

对照实验室研究。

方法

在48例患者(37例退变性撕裂和11例创伤性撕裂)进行临床指征的部分半月板切除术时,从半月板白区切除撕裂半月板的样本。通过定量实时聚合酶链反应测量损伤半月板中骨关节炎、炎症和软骨稳态的选定分子标志物(如细胞因子/趋化因子、聚集蛋白聚糖酶/金属蛋白酶、转录因子、软骨基质基因和脂肪因子)的mRNA表达。记录每位患者的撕裂模式(创伤性或退变性)和位置(内侧或外侧)。在调整患者的年龄、性别和体重指数以及切除半月板的位置(内侧/外侧)后,计算退变性和创伤性撕裂之间的基因表达差异。

结果

半月板撕裂中的基因表达因模式而异。与退变性撕裂相比,趋化因子(IL8 [P <.001]和CXCL6 [P <.001])和基质金属蛋白酶(MMP1 [P =.011]和MMP3 [P =.016])在创伤性撕裂中的表达水平显著更高。相比之下,与退变性撕裂相比,COL1A1在创伤性撕裂中的表达水平较低(P =.058)。所测试的基因在半月板内侧和外侧撕裂之间均未显示出显著差异。

结论

创伤性半月板撕裂总体上表现出比退变性撕裂更高的炎症/分解代谢反应,趋化因子和基质金属蛋白酶表达水平更高证明了这一点。这些发现表明创伤性和退变性撕裂之间存在(分子)生物学差异。

临床意义

创伤性和退变性撕裂之间的分解代谢/炎症差异可能与半月板的治疗决策相关,也有助于我们进一步了解半月板撕裂与膝关节骨关节炎发展之间的关系。

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