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

Identification of ageing biomarkers in human dermis biopsies by thermal analysis (DSC) combined with Fourier transform infrared spectroscopy (FTIR/ATR)

Background/purpose : The purpose of this clinical study was to identify suitable biomarkers for a better understanding of the molecular and organizational changes in human dermis during intrinsic and extrinsic ageing. Methods : Sun-exposed and non-exposed skin biopsies were collected from twenty-eight women devised in two groups (20-30 and ≥60 years old). The hydric organization and thermal transitions were determined by Differential Scanning Calorimetry (DSC). Fourier Transform Infrared spectroscopy (FTIR) was used to identify the absorption bands of the dermis and to quantify the different absorbance ratio. Results : The amounts of total, freezable and unfreezable water were determined. A significant increasing amount of freezable water is evidenced in sun-exposed area skin of aged group compared with young group (P=.0126). Another significant effect of extrinsic ageing (P=.0489) is the drastic decrease of fibrillary collagen, the main protein component of dermis. The only significant effect of intrinsic ageing (P=.0184) is an increase of the heat-stable fraction of collagens in dermis. Conclusion : DSC and FTIR are well-suited techniques to characterize human skin, giving accurate results with a high reproducibility. The combination of these techniques is useful for a better understanding of human skin modifications with intrinsic and extrinsic ageing

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

JAK/STAT but Not ERK1/ERK2 Pathway Mediates Interleukin (IL)-6/Soluble IL-6R Down-regulation of Type II Collagen, Aggrecan Core, and Link Protein Transcription in Articular Chondrocytes

International audienc

Role of interleukin 6 (IL-6)/IL-6R-induced signal tranducers and activators of transcription and mitogen-activated protein kinase/extracellular.

Studies have described elevated levels of interleukin 6 (IL-6) and its soluble receptor (sIL-6R) in osteoarthritic and rheumatoid joints, as well as the inhibitory effect of this combination on cartilage matrix production. We investigated the ability of IL-6/sIL-6R to modulate gene expression of matrix metalloproteinase (MMP) and ADAMTS (ADAMS with thrombospondin motifs) family members in bovine chondrocytes, and the potential role of signal transducers and activators of transcription (STAT) and mitogen-activated protein kinases (MAPK) in this regulation