Development and characterization of various osteoarthritis models for tissue engineering

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Abstract

Osteoarthritis (OA) is characterized by a progressive loss of articular cartilage, subchondral bone sclerosis and synovial inflammation and is the most common chronic condition worldwide today. However, most treatments have focused on pain relief and OA symptoms. For these reasons, many ongoing studies are currently trying to develop efficient and successful therapies based on its pathology. Animal models that mimic the histopathology and symptoms of OA have a critical role in OA research and make it possible to investigate both secondary osteoarthritic changes due to a precedent event such as traumatic injury and naturally occurring changes for the development of therapeutics which can be tested in preclinical and clinical OA trials. We induced OA in various animal models including rats, rabbits and Guinea pigs by chemical, surgical and naturally occurring methods. In particular, the Dunkin-Hartley Guinea pig is very attractive as an OA animal model because OA slowly progresses which is similar to human primary OA. Thus, this animal model mimics the pathophysiological process and environment of human primary OA. Besides the spontaneous OA model, anterior cruciate ligament transection (ACLT) with medial meniscectomy and bilateral ovariectomy (OVX) as well as a chemical technique using sodium monoiodoacetate (MIA) were used to induce OA. We found that ACLT in the rat model induced OA changes in the histology and micro-CT image compared to OVX. The osteoarthritic change significantly increased following ACLT surgery in the rabbit model. Furthermore, we identified that OA pathogenic changes occurred in a time-dependent manner in spontaneous Dunkin-Hartley Guinea pigs. The MIA injection model is a rapid and minimally invasive method for inducing OA in animal models, whereas the spontaneous OA model has a slow and gradual progression of OA similar to human primary OA. We observed that histological OA change was extraordinarily increased at 9 1/2 months in the spontaneous OA model, and thus, the grade was similar with that of the MIA model. Therefore, this study reports on OA pathology using various animal models as well as the spontaneous results naturally occurring in an OA animal model which had developed cartilage lesions and progressive osteoarthritic changes.

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Kim, J. E., Song, D. H., Kim, S. H., Jung, Y., & Kim, S. J. (2018). Development and characterization of various osteoarthritis models for tissue engineering. PLoS ONE, 13(3). https://doi.org/10.1371/journal.pone.0194288

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