Abstract: Osteoarthritis (OA) is characterized by a progressive degradation of cartilage and loss of joint function.
A simple and reproducible animal model that mimics molecular and pathological changes in the articular cartilage
of knee joint OA would help in understanding its pathophysiological mechanism and aid in the preclinical
assessment of disease modifying drugs. The aim of our study is to evaluate changes in Aggrecan gene expression
as a part of molecular events underlying cartilage turnover in monosodium iodoacetate (MIA)-induced knee OA
through determination of aggrecan mRNA expression and immunostaining and its relation to disease chronicity
and severity. OA was induced by single intra-articular injection of MIA into knee joints of male rats. Histologic
and molecular changes in the knee cartilage were evaluated by light microscopy, real-time PCR and
immunohistochemistry. Our results showed that injection of an MIA induced typical OA-like lesions in the knee
joint within 3 weeks. Furthermore, there was a significant down-regulation of aggrecan gene expression in MIAinduced
OA in a time dependent manner, and that reflects the severity of OA in terms of Mankin score. These
results were confirmed through estimation of aggrecan content in cartilage by immunohistochemical analysis,
which revealed a progressive decrease in aggrecan immunoexpression. In conclusion, intra-articular MIA
injection is an animal model that presents reliable profiling of the sequence, chronic and complex nature of OA.
This would help studying the OA modifying drugs specially those suggested having anabolic effect and enhancing
the PG contents both at early and late stages of the disease.