Evaluation of effectiveness of different bioactive agents for treatment of osteoarthritis with in vitro model under dynamic mechanical stimulation


Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Mühendislik Fakültesi, Mühendislik Bilimleri Bölümü, Türkiye

Tezin Onay Tarihi: 2007

Öğrenci: AYŞEGÜL KAVAS

Eş Danışman: AYŞEN TEZCANER, DİLEK KESKİN

Özet:

Osteoarthritis (OA) is a disease characterized by the progressive degradation of articular cartilage. Current strategies for the disease are mainly towards relieving symptoms. This study was aimed to investigate the therapeutic potentials of Bone Morphogenetic Protein-9 (BMP-9), Raloxifene (Ral) and Pluronic F-68 (PLF-68) with a three-dimensional in vitro OA model. Articular chondrocytes isolated from rats were cultured in growth media and embedded in agarose to obtain agarose-chondrocyte discs. Dynamic hydrostatic mechanical stress was applied to discs. The discs were incubated with Aza-C for 48 hours for OA development. After its removal, chondrocytes were treated with different doses of BMP-9, Ral and PLF-68 for 10 days. The efficacies of treatments were evaluated by measuring cell number, glycosaminoglycan and collagen amount, and mechanical properties of the v discs. Measurements of these properties were performed with MTT, quantitative colorimetric assays, histochemical staining and mechanical tests, respectively. According to comparative results with healthy groups and controls (osteoarthritic chondrocytes without any treatment), it was found that BMP-9 had negative effect on osteoarthritic chondrocytes. On the other hand, Ral showed positive results related with matrix synthesis and mechanical properties especially at 5 μM dose suggesting that it holds promise for the treatment of OA. The therapeutic effect of Ral on OA was documented for the first time in literature. The potential of PLF-68 for treatment of OA was also supported by this study considering its positive effects on cell number, collagen synthesis and mechanical properties. Yet, further investigations are also suggested for conclusive results on this agent.