The protective effect of licofelone on experimental osteoarthritis is correlated with the downregulation of gene expression and protein synthesis of several major cartilage catabolic factors: MMP-13, cathepsin K and aggrecanases

Along with the graying of the world's population, osteoarthritis (OA), the most common form of arthritis, is becoming an increasingly significant medical and financial burden. In this context, the clear need for a better understanding of the disease process has rendered undeniable the importance of finding drugs that can reduce or stop its progression.Recent studies have revealed new and interesting information regarding the role played by eicosanoids in the pathophysiology of arthritic diseases, including OA [1-6]. For instance, leukotriene-B4 (LTB4) has proven to be an important regulating factor in the synthesis of IL-1β by OA synovium [6-8]. Both in vitro and in vivo studies have demonstrated that the excess production of IL-1β in OA tissue is a key factor in its destruction and in the progression of the disease itself [1,9]. The endogenous production of LTB4 in OA synovium is a crucial element in the upregulation of IL-1β synthesis in this tissue [8]. The synthesis of LTB4, and subsequently of IL-1β, can be significantly increased by non-steroidal anti-inflammatory drugs (NSAIDs) [10,11]. It has been hypothesized that this could be related to a 'shunt' of the arachidonic acid cascade from the cyclooxygenase (COX) to the lipoxygenase (LOX) pathway [2]. These findings could help explain how some NSAIDs accelerate the progression of clinical OA [12]. A recent study from our laboratory has demonstrated that, in in vivo experimental OA, licofelone, a drug that can inhibit both the COX and 5-LOX pathways, was capable of reducing the development of OA structural changes while simultaneously reducing the synthesis of LTB4 and IL-1β by the OA synovium [6]. These findings are in strong support of the in situ role played by LTB4 in the structural changes that occur in OA.The progression of the structural changes that occur during the course of the disease is related to a number of complex pathways and mechanisms, among which the excess production of proteolytic enzymes th