Forsøksdyr: The effect of miR-140 on inflammation and its potential as a therapeutic agent for Osteoarthritis

Godkjenningsdato 01.10.2018

Godkjenningsperiode 01.10.2018-01.12.2019

The aim of this study is to investigate the potential protective effects of miR-140 (MicroRNA-140; microRNAs are small non-coding RNAs that regulate gene expression) against osteoarthritis (OA). Further we would like to know whether these effects are of significantly high impact to allow miR-140 to be applied in therapy for humans suffering from OA, or for those who are in danger of developing the disease.
OA is a common disease, affecting 12% of the population above 30 years of age; more prevalent in the elderly, in women, in persons with previous injury to articular cartilage and in persons with a family history of OA(1-3). The exact causes of OA are not known, but some factors associated with the disease are age, trauma, obesity, inflammation, genetics and joint pathologies. Currently there are no disease modifying therapeutic approaches for OA. Treatment options are directed towards reducing symptoms and include non-pharmaceutical measures such as physical exercise and weight loss, analgesics, non-steroidal anti-inflammatory agents or intra-articular injection of steroids and hyaluronic acid. Because there is no treatment available today that can stop or reverse the development of OA, the final outcome of OA is joint replacement. In Norway alone more than 5 000 prosthesis operations are performed every year (8). Patients suffering from OA describe a life of pain with high consumption of analgesics, limited mobility and consequently unstable work performance, all of which is contributing to a decreased quality of life for the patients and a great economical burden for the society. Thus developing a therapeutic approach that could be used in early stages of the disease would be of great value to the patients, their families and the society as a whole.
In this experiment, we would like to use the Dunkin Hartley strain of guinea pigs. These animals all develop OA spontaneously, with every animal showing histopathological signs of moderate OA at 12 months of age. This model would be very similar to the spontaneous development of OA in many humans, particularly as guinea pigs are the animal species in which cartilage morphology is most similar to human cartilage. The treatment is expected to reverse the development of OA, leaving the treated animals with disease-free joints and no symptoms of painful OA. The experiment will be characterized as “moderat belastende".
In order to obtain meaningful results, we would need to perform the experiments on 44 guinea pigs. The design of this study has been done to minimize the number of guinea pigs required based on the 3R’s “Replacement, Reduction, Refinement”. For example, guinea pigs will be obtained externally at 3 months of age, thus avoiding the requirement to establish a breeding program at the facility, and initial pilot experiments will be performed on already available guinea pig cadavers.