Osteoarthritis (OA) is the most common rheumatic disease, and its medical relevance is rising in the Western population, mainly in people over 65. 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 effects of some nutraceuticals on chronic-inflammation pathways altered in synoviocytes in order to find inhibitors, specific for OA. Previously, we showed that Glucosamine has anti-inflammatory activity in OA chondrocytes, by inhibiting the AP-1 and NF-kB pathways. We will explore the possible anti-inflammatory effects of this molecule on synoviocytes. We will study also the effects Harpagophytum extract on these cells with particular attention to anti-nociceptive pathways. In particular, we are going to explore the intracellular pathways associated with CB2 receptor, such as the activation of inhibitory protein G (Gi), the downregulation of cyclic AMP (cAMP) and the phosphorylation of kinases, as Extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38).
Finally, we will analyze the effects of contemporary administration of glucosamine and Harpagophytum extract, considering the anti-inflammatory activity of glucosamine on chondrocytes and the possible anti-nociceptive activity of Harpagophytum extract, we expect a synergistic effects on synoviocytes.
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.