Item – Theses Canada

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OCLC number
1006927799
Link(s) to full text
LAC copy
LAC copy
Author
Hellio Le Graverand-Gastineau, Marie-Pierre.
Title
Molecular and cell biology of rabbit menisci and articular cartilage of the knee : a model of osteoarthritis.
Degree
Ph. D. -- University of Calgary, 2000
Publisher
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, 2001.
Description
3 microfiches
Notes
Includes bibliographical references.
Abstract
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.
ISBN
0612547876
9780612547872