Stimulating effect of diacerein on TGF-β1 and β2 expression in articular chondrocytes cultured with and without interleukin-1

AbstractObjective: Diacetylrhein or diacerein has shown efficacy in the treatment of both major forms of osteoarthritis (OA), coxarthrosis as well as gonarthrosis, improving clinical symptoms of the disease (pain reduction and algo-functional index). Both in-vitro and animal models studies suggest that diacerein may have also disease-modifying effects. The drug exerts inhibitory effects on interleukin-1-induced expression of cartilage degrading enzymes. However, its mechanism of action is not completely understood. In view of the role that could play the transforming growth factor (TGF)-β system in the repair potentialities of OA cartilage, we studied the effect of diacerein on the expression of TGF-β isoforms 1, 2 and 3 and that of their receptor types I and II in cultured bovine chondrocytes.Methods: Cultured bovine articular chondrocytes were treated with 10−5mdiacerein, 10ng/ml IL-1β or the combination diacerein+interleukin (IL)-1, and the expression of both TGF-β isoforms 1, 2 and 3 and that of their receptors TβR-I and TβR-II was determined by Northern-blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Cell transfections of cDNA constructs containing sequences of the 5′-upstream region of TGF-β1 promoter were also performed to determine their transcriptional activity in diacerein-treated cultures.Results: The data indicated that diacerein enhances the expression of TGF-β1 and TGF-β2. This effect was also found in the presence of IL-1, albeit with smaller intensity. In contrast, the levels of TGF-β3 and receptors I and II remained unaffected or slighty modified by the compound. Treatment of cells transiently transfected with TGF-β1 promoter constructs suggested that the stimulating effect on TGF-β1 expression is mediated by the region −1038 to −1132base pars.Conclusion: The results suggest that diacerein effects on matrix synthesis and turn-over previously reported in cultured articular chondrocytes might be explained in part by the ability of the drug to enhance TGF-β1 and TGF-β2 expression in these cells. This mechanism of action may account for the potential disease-modifying properties of diacerein and might give clues as to how future anti-osteoarthritic drugs should be designed

BLUEMED. Marine and Maritime RTDI Strategies

In the framework of the BLUEMED project, the coordination action supporting the development of the BLUEMED Research and Innovation Initiative for blue jobs and growth in the Mediterranean area (www.bluemed-initiative.eu/), an overview and analysis of funding schemes available at different levels, from national to European and international, has been carried out. This task is part of the activities devoted to strengthening cooperation to consolidate and implement the BLUEMED Strategic Research and Innovation Agenda (SRIA). It complements the BLUEMED interconnecting Platforms developed by the four BLUEMED operational working groups on knowledge, economy, technology and policy, to update the SRIA and serves as reference tool in the process of developing an operational network of research funders and key players to favour synergies and coordinate the realization of the BLUEMED actions. This report can be considered a background document to initiate and facilitate dialogue and interaction between research funding agencies of different countries and European Institutions. Once the strategic alignment of agendas on areas of mutual interest has been identified, the aim is to lay the groundwork for operational alignment towards the launch of transnational actions. As a first step, a catalogue (Annex I and II) has been compiled for reviewing marine and maritime RTDI strategies. The collected information has been analysed to address opportunities of alignment for joint implementation of the BLUEMED SRIA (section 2) and finally provide a set of preliminary recommendations to develop the BLUEMED Implementation plan (section 3), one of the key deliverables of the project