For several years we have been researching the mechanisms involved in inflammatory processes. Our research has focused on a number of aspects such as the study of the decisive mediators of the progression of joint injuries, the possible mechanisms for protection and the main key signaling pathways involved, to better understand the pathogenesis of inflammatory diseases and find new therapeutic targets.
To study them we conduct in vivo and in vitro studies. We use different animal models of acute inflammation (air pouch in rats and mice, carrageenan edema, skin inflammation, intestinal inflammation) and chronic inflammation, such as models of rheumatoid arthritis (adjuvant arthritis, collagen arthritis, arthritis by serum transfer in K/BxN transgenic mice). We have developed models of age-related degenerative osteoarthritis such as spontaneous arthritis in STR/ort mice, following the temporal evolution of the disease, with biochemical studies of biomarkers in serum and joint tissues, and by means of radiological, histological, and other. studies. All these findings allow us to relate the onset and progression of the lesions as the animal ages and propose various mechanisms that can regulate these processes. We have also developed animal models of osteoporosis in rats (ACLT + ovariectomy) and mice (CIA + ovariectomy).
We have conducted studies in cartilage explants, chondrocytes, synoviocytes and osteoblasts from osteoarthritic patients, to determine gene expression and protein factors that may be related to the disease progression. We have determined the consequences of the over-expression (by transfection with adenovirus) or inhibition (gene silencing with siRNA) of these factors on cell metabolism, synthesis and degradation of extracellular matrix components, production of cytokines, chemokines , factors of growth and cell differentiation, eicosanoids, reactive species, etc. We have also studied the signaling and transcriptional pathways related to these factors. Studies from our group have shown a protective role of heme oxygenase-1 against cell stress in different cell types and in vivo models.
We have carried out studies in fibroblasts and keratinocytes of healthy patients and of psoriatic patients to determine the inflammatory mediators and the mechanisms involved in this pathology. We have also conducted in vitro cell studies in human microendothelial cell models, fibroblasts and keratinocytes, focusing on adenosine as a target that may allow to find new therapeutic strategies for wound healing in highly susceptible population groups such as the diabetic, the obese and the elderly.
Using the aforementioned experimental models we have evaluated different groups of anti-inflammatory drugs, some of them analogues of marine products. In this line we created a patent for cacospongionolida B, as a new anti-inflammatory inhibitor of phospholipase A2, in collaboration with the CNR of Italy. Recently, we have studied new inhibitors of microsomal Prostaglandin-E synthase in various models.