A human osteoarthritis mimicking goat cartilage explant-based disease model for drug screening

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Arijit Bhattacharjee
Dhirendra Katti


Osteoarthritis (OA) is the most prevalent human joint disease with a massive global disease burden. Despite having a large socioeconomic burden, OA remains a neglected disease with no clinically approved disease modifying therapies. One of the key reasons for this is that the available disease models poorly recapitulate human OA-like traits possibly because of the challenge of mimicking the disease in an ECM rich cartilage tissue. Therefore, in this study, we report the establishment and validation of a clinically relevant ex vivo OA model using IL1β treated goat articular cartilage explants. Treatment with IL1β induced OA-like traits in goat cartilage explants and caused a shift in cartilage homeostasis towards enhanced catabolism, resulting in higher matrix degradation, overexpression of degradative and inflammatory mediators and chondrocyte hypertrophy. We then validated the developed disease model for drug response using three different drugs viz. BMP7, rapamycin and celecoxib, all of which demonstrated concentration-dependent disease amelioration in the explant model. Finally, we evaluated the translational relevance of the developed ex vivo OA model by comparing it with late-stage OA patient samples and observed a striking resemblance in terms of matrix degradation, expression of degradative enzymes, chondrocyte hypertrophy and inflammation. Overall, the goat ex vivo OA model elicited a biological response to cytokine treatment which mirrors human OA-like traits that may reduce discordance between preclinical and clinical studies in OA drug development.

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Bhattacharjee, A. and Katti, D. (2022) “A human osteoarthritis mimicking goat cartilage explant-based disease model for drug screening”, ALTEX - Alternatives to animal experimentation. doi: 10.14573/altex.2107071.

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