الفهرس 
Acknowledgement
(Osteoarthritis (OAOnly 14 pages are availabe for public view
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Abstract
Recently, SR is considered as a one of the DMOADs. However, until now there has been a lack of data regarding the cartilage turnover in OA during treatment with SR. Moreover, the direct effect of SR on the major proteoglycan metabolism of articular cartilage is still unclear. Therefore, this study investigates whether articular cartilage degeneration in experimental OA could be attenuated during treatment with SR through molecular mechanism. This was assessed by establishment of an experimental model (monosodium iodoacetate-induced OA rat) that mimics the cartilage lesion associated with human OA and determination of aggrecan mRNA expression in the articular cartilage before and after SR treatment. In addition, the aggrecan loss was estimated by determination of aggrecanase-2 (ADAMTS-5) mRNA expression during the study.
Immunohistochemical analysis of articular cartilage was also performed to detect the change of aggrecan content in MIA-induced OA rats by SR treatment in addition to histopathological study for estimating cartilage thickness, investigating total proteoglycan content and to confirm the biochemical changes along the study.
Sixty one male albino rats (200-220 g), aged 8-12 weeks were used in this study. Rats were assigned randomly and divided into the following groups:
1. Control group: 7 normal untreated rats kept fed on normal healthy conditions.
2. Vehicle group: 7 rats given single intra-articular injection of sterile saline in the left knee joint (the vehicle of MIA).
3. MIA-induced osteoarthritis group (MIA3): 7 rats given single intra-articular injection of 50 µl MIA (60 mg/ml) in the left knee joint received no treatment and sacrificed 3 weeks post injection.
4. SR- treated and corresponding groups:
i- SR- treated group for 3 weeks (MIA3-SR3): 10 rats given single intra-articular injection of 50 µl MIA (60 mg/ml) in the left knee joint, 3 weeks later, they treated orally with SR (1800mg/kg/ day) for another 3 weeks.
Corresponding untreated group (MIA6): 10 rats given single intra-articular injection of 50 µl MIA (60 mg/ml) in the left knee joint received no treatment and sacrificed 6 weeks post injection.
ii- SR- treated group for 6 weeks (MIA3-SR6): 10 given single intra-articular injection of 50 µl MIA (60 mg/ml) in the left knee joint , 3 weeks later, they treated orally with SR (1800mg/kg/ day) for another 6 weeks
Corresponding untreated group (MIA9): 10 rats given single intra-articular injection of 50 µl MIA (60 mg/ml) in the left knee joint received no treatment and sacrificed 9 weeks post injection.
The results of the present study showed significant downregulation of gene expression of aggrecan while significant upregulation of ADAMTS-5 gene in all untreated MIA- induced OA animal groups when compared to control. However, SR treatment was found to downregulate ADAMTS-5 and upregulate of aggrecan gene expressions in SR treated MIA- induced OA animal groups compared to their corresponding groups. Also SR treatment for 6 weeks significant upregulated aggrecan gene expression in compared to MIA3 group. These results were strongly confirmed through estimation of aggrecan content in cartilage by immunohistochemical analysis and histopathological study of knee joint cartilage of different groups.
Regarding immunohistochemical results, there was progressive decrease in aggrecan positive reaction in untreated MIA-induced OA groups (MIA3, MIA6 and MIA9 groups), While SR treated groups showed marked increase in positive reaction of aggrecan in comparison to untreated OA groups. Also, SR was also found to increase cartilage thickness, increase PG content and reduce histopathological lesion score (Mankin score) when administered to MIA-induced OA rats as detected by histopathological examination.
Conclusion:
In conclusion, the current investigations showed that administration of SR ameliorated knee cartilage lesions in MIA-induced OA rat model. This was evidenced by reduction of swelling and limping as well as increasing cartilage thickness potentially via upregulation of aggrecan mRNA expression. Moreover, SR attenuated aggrecan loss in articular cartilage of MIA-induced OA rats by downregulating ADAMTS-5 mRNA expression and thus slows progressive cartilage erosion. These findings were proved and confirmed by histopathological and immunohistochemical studies.