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Molecular and cell biology of rabbit menisci and articular cartilage of the knee: A model of osteoarthritis.

机译:兔半月板和膝关节软骨的分子和细胞生物学:骨关节炎的模型。

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摘要

Osteoarthritis (OA) is the most common and costly form of arthritis. The overall objective of this dissertation was to characterize an animal model of osteoarthritis that would increase our understanding of disease development and be useful for studying potential OA modifying drugs. The experiments were designed to examine the regulation of connective tissues of the knee and the response of articular cartilage and menisci to knee instability following transection of the ACL in rabbits. The outcome parameters of these experiments were assessed via semi-quantitative RT-PCR, histology and immunohistochemical techniques. The characterization of specific changes was assessed for each one of the connective tissues studied [i.e., menisci (MM, LM), and articular cartilage (LFC, MFC, LTP and MTP)] in response to skeletal maturation, hormonal changes, and injury.;In the first experiment, transcript levels in the medial and lateral menisci were assessed during tissue maturation. Maturation altered mRNA levels for several of the molecules studied. In addition, significant differences between the medial and lateral menisci were observed regardless of skeletal maturity. The medial meniscus always expressed significantly higher mRNA levels compared to the lateral meniscus. In the second set of experiments, transcript levels in the medial and lateral menisci, as well as in four articular cartilage surfaces were assessed during pregnancy. Pregnancy altered mRNA expression modestly within both the medial and lateral menisci compared to articular cartilage. In addition, mRNA modifications were tissue-specific (i.e., MM vs LM, as well as LFC vs MFC vs LTP vs MTP). In the third set of experiments, the response of menisci and articular cartilage to ACL transection indicated the early development of reproducible lesions in the medial compartment of the rabbit knee in response to joint instability. In the medial meniscus, significant structural as well as molecular and biochemical changes occurred following ACL transection. In the MTP and MFC, similar changes were observed.;These studies emphasize the importance of understanding meniscal homeostasis and pathogenesis within the knee joint in order to help maintain proper joint function. In addition, the present characterization of the rabbit model of osteoarthritis induced by ACL transection demonstrates its usefulness in improving basic knowledge of osteoarthritis pathophysiology, as well as providing some significant tools to address the pressing clinical problem of effectively treating the disease.
机译:骨关节炎(OA)是关节炎最常见和最昂贵的形式。本文的总体目标是表征一种骨关节炎的动物模型,该模型将增加我们对疾病发展的了解,并有助于研究潜在的OA修饰药物。实验旨在检查兔ACL横断后膝关节结缔组织的调节以及关节软骨和半月板对膝关节不稳定的反应。通过半定量RT-PCR,组织学和免疫组化技术评估了这些实验的结果参数。针对骨骼成熟,荷尔蒙变化和损伤,对研究的每种结缔组织[即半月板(MM,LM)和关节软骨(LFC,MFC,LTP和MTP)]评估特定变化的特征。 ;在第一个实验中,在组织成熟过程中评估内侧和外侧半月板的转录水平。成熟改变了几个研究分子的mRNA水平。此外,无论骨骼成熟度如何,内侧半月板和外侧半月板之间均存在显着差异。与外侧半月板相比,内侧半月板始终表达显着更高的mRNA水平。在第二组实验中,在怀孕期间评估了内侧和外侧半月板以及四个关节软骨表面的转录水平。与关节软骨相比,妊娠在内侧和外侧半月板内均适度改变了mRNA表达。另外,mRNA修饰是组织特异性的(即,MM对LM,以及LFC对MFC对LTP对MTP)。在第三组实验中,半月板和关节软骨对ACL横断的反应表明,响应关节不稳,兔膝内侧腔可再现性病变的早期发展。在内侧半月板中,ACL横断后发生了明显的结构以及分子和生化变化。在MTP和MFC中,观察到了类似的变化。这些研究强调了了解膝关节半月板稳态和发病机制的重要性,以帮助维持适当的关节功能。此外,通过ACL横切术诱发的兔骨关节炎模型的当前特征证明,它在改善骨关节炎病理生理学基础知识方面是有用的,并提供了一些重要工具来解决有效治疗该疾病的紧迫临床问题。

著录项

  • 作者单位

    University of Calgary (Canada).;

  • 授予单位 University of Calgary (Canada).;
  • 学科 Biology Molecular.;Health Sciences Pathology.;Biology Animal Physiology.
  • 学位 Ph.D.
  • 年度 2000
  • 页码 267 p.
  • 总页数 267
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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