Osteoarthritis (OA) is the most common rheumatic disease, and its medical relevance is rising, in the Western population 1 out 3 people over 65 are OA patients. This pathology is characterized by progressive destruction of the extracellular matrix (ECM), causing pain and disability in patients. In the last decades, a growing importance has been given to the chronic and low-grade inflammation in OA etiology.
To date, OA is a non-curable disease, it is treated with analgesic agents, anti-inflammatory and painkiller drugs, mainly non-steroidal anti-inflammatory drugs (NSAIDs), with the aim to alleviate the symptoms. Some disease-modifying OA drugs (DMOADs) are also administered to OA patients, with partially inconsistent results, for this reason, a substantial need remains for safe and effective DMOADs.
The aim of this project is to analyze the synovial fluid and synovial lining coming from OA and non-OA (traumatic fracture) patients, who underwent to prosthesis surgery. In order to verify whether there are gender differences, samples will be obtained both by male and female patients. In the synovial fluid, the presence of immune system cells will be checked by flow cytometry analyses, the upregulation of specific pattern-related receptors (PRRs) and cannabinoid receptor-2 (CB2) will be analyzed by immunoistochemistry. In the second part of the project, synoviocytes will be isolated and they will be used as in vitro model to analyze the effects of some nutraceuticals on pathways altered in low- chronic- inflammation, with the aim to find low-grade inflammation inhibitors, specific for OA.
The innovative aspects of this project are at least three.
The first aspect regards the topic, considering that the central role of inflammation in OA has been highlighted only in the recent years, the studies conducted so far did not yet reached conclusive results able to consent to formulate appropriate anti-inflammatory therapies. Moreover, the analyses of the synovial fluid from a large number of patients, coming from different countries in the world allow to reach more conclusive results. To our knowledge, in Italy studies regarding the analysis of the synovial fluid has not been conducted.
The second aspect regards the search of natural compounds able to contrast the inflammation. To date, the OA patients are treated mainly with NSAIDs drugs, which cause side effects, especially considering that they are to be administered for very long periods. The NSAIDs contrast the symptoms but they are not curative, for this reason a substantial need remains for safe and effective disease-modifying OA drugs (DMOADs).
Finally, the in vitro molecule screening system, using human primary cells, should be emphasized as an aspect of innovation. In vitro screening allows to avoid, at least in the initial stages, studies in animals, in accordance with the European Community regulations on clinical trials.