Early changes in lapine menisci during osteoarthritis development - Part II: Molecular alterations
Early changes in lapine menisci during osteoarthritis development - Part II: Molecular alterations
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DOI：
10.1053/joca.2000.0351
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发表时间：
2001-01-01
影响因子：
7
通讯作者：
Hart, DA
中科院分区：
文献类型：
--
作者：
Le Graverand, MPH;Vignon, E;Hart, DA
目的：骨关节炎（OA）是关节炎的最常见形式，并且膝关节的踝关节和韧带损伤的患者处于发展该疾病的高风险中。本研究的目的是评估前交叉韧带（ACL）横断兔膝关节在术后3周和8周时内侧和外侧韧带的变化。本研究介绍了分子和细胞的变化在rabci在早期阶段的OA development.Design：兔rabbit组织进行了处理的分子分析：DNA和RNA浓度进行了评估，以及半定量逆转录-聚合酶链反应（RT-PCR）分析的一个子集的相关分子进行。原位DNA片段进行了评估，使用TUNEL assay.Results：总RNA产量从内侧半月板显着升高，在3和8周后ACL横断，而在外侧半月板总RNA水平不变后ACL横断。仅在ACL横断后8周，内侧韧带的DNA浓度显著降低。ACL横断后，原位DNA片段化分析使用TUNEL法表明，在内侧半月板中的凋亡细胞的数量增加，特别是在ACL横断后3周，这一发现与DNA含量下降相关。通过RT-PCR对特定mRNA水平的分析表明，ACL横断后两个ACL的变化复杂。在ACL横断后3周和8周，在内侧和外侧ACL中，I型胶原和TIMP-1的mRNA水平显著增加，而核心蛋白聚糖、TNF-α和IGF-2的mRNA水平显著降低。在内侧半月板中，在两个时间段检测到I）型胶原、双糖链蛋白聚糖以及iNOS和PAI-1的mRNA水平显著增加，而聚集蛋白聚糖、III型胶原和考克斯-2的mRNA水平在ACL横断后3周显著升高，MMP-1的mRNA水平在ACL横断后8周显著升高。相反，ACL横断后外侧半月板中COL 2和聚集蛋白聚糖的mRNA水平没有变化。在外侧半月板，在3周后ACL横断，III型胶原mRNA水平显着增加，而纤调蛋白mRNA水平显着抑制。在外侧半月板？在ACL横断后8周检测到双糖链蛋白聚糖mRNA水平的显著增加。结论：这些结果表明，ACL横断后，复杂的分子变化，以及细胞凋亡，早期发生，特别是在内侧半月板。(C)2001年国际骨关节炎研究学会。
Objective: Osteoarthritis (OA) is the most common form of arthritis and patients with meniscal and ligament injuries of the knee are at high risk to develop the disease. The purpose of this study was to evaluate changes occurring in both medial and lateral menisci from the knees of anterior cruciate ligament (ACL) transected rabbits at 3 and 8 weeks post-surgery. This study describes both molecular and cellular alterations in menisci during the early stages of OA development.Design: Rabbit meniscal tissues were processed for molecular analysis: DNA and RNA concentrations were assessed, as well as semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for a subset of relevant molecules was performed. In situ DNA fragmentation was evaluated using the TUNEL assay.Results: Total RNA yields from the medial meniscus were significantly elevated at both 3 and 8 weeks post-ACL transection, while in the lateral meniscus total RNA levels were unchanged following ACL transection. DNA concentrations were significantly decreased in the medial menisci only at 8 weeks post-ACL transection. Following ACL transection, analysis of in situ DNA fragmentation using the TUNEL assay demonstrated an increase in the number of apoptotic cells in the medial meniscus only, in particular at 3 weeks post-ACL transection, a finding which correlates with declines in DNA content. Analysis of specific mRNA levels by RT-PCR demonstrated complex changes in both menisci following ACL transection. At 3 and 8 weeks post-ACL transection, in both medial and lateral menisci, mRNA levels for type I collagen and TIMP-1 were significantly increased, while mRNA levels for decorin, TNF-alpha and IGF-2 were significantly depressed. In the medial meniscus, significant increases in mRNA levels for type I) collagen, biglycan as well as iNOS and PAI-I were detected at both time periods, while mRNA levels for aggrecan, type III collagen and COX-2 were significantly elevated at 3 weeks post-ACL transection and mRNA levels for MMP-1 were significantly elevated at 8 weeks post-ACL transection. In contrast, mRNA levels for COL2 and aggrecan were unchanged in the lateral meniscus following ACL transection. In the lateral meniscus, at 3 weeks post-ACL transection, type III collagen mRNA levels were dramatically increased while fibromodulin mRNA levels were significantly depressed. In the lateral meniscus? significant increases in mRNA levels for biglycan were detected at 8 weeks post-ACL transection.Conclusion: These results show that after ACL transection complex molecular changes, as well as apoptosis, occur early, particularly in the medial meniscus. (C) 2001 OsteoArthritis Research Society International.