This study shows that in vitro in chondrocytes, BMP9 potently induces pSmad1/5 and a chondrocyte hypertrophy-like state, which is potently blocked by TGFβ1. This observation underlines the importance of TGFβ1 in maintenance of chondrocyte phenotype.

We identified a relationship between IL-37 and reduced sGAG loss in OA cartilage. Most likely, this effect is mediated by inhibition of MMP-3 expression. These results suggest that IL-37 could be applied as therapy in a subgroup of OA patients, in which cartilage degradation is mediated by MMP-3.

IL37 is induced by IL1β, and IL37 itself reduced IL1β, IL6 and IL8 production, indicating that IL37 is able to induce a counter-regulatory anti-inflammatory feedback loop in chondrocytes. In addition, IL37 dampens catabolic enzyme expression. This supports IL37 as a potential therapeutic target in OA.

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Purpose:We have previously identified that synovial lubricin, involved in the lubrication in cartilage lubrication of the joints, is sulfated. This sulfation is covalently attached to the highly glycosylated mucin domain of lubricin and has been indicated to interfere with inflammatory responses in the joint tissue. In order to exploit this furher, we are interested in idenifying the enzymes involved in the altered glycosylation. This would help us to genarate glyco versions of lubricin to explore the functional consequences of altered lubricin during inflammation. Methods: Recombinant expression of O-linked glycoprotein oligosaccharides was performed in chinese hamster ovary (CHO) cells. Sulfation and elongation of the CHO cells commonly expressed core 1, Galb1-3GalNAc, oligosaccharides were performed using human core 2 and elongation core 1 GlcNAc transferases together with sulfotranferases specific for 3 linked and 6 linked sulfation. O-linked oligosaccharides were released from reccombinant mucin glycoprotein carrier an analysed using graphitized carbon chromatography coupled to mass spectrometry. Results: By transfection of CHO cells with sulfotransferases and GlcNActransferarses we could show that we could mimic the sulfation found on lubricin in normal an inflammed states. This included the unusual sulfation of core 1 O-linked oligosaccharides and the more ubiquitously expressed 6 linked sulfation on core 2 O-linked structures. Conclusions: Sulfation of O-linked oligosaccharides on lubricin is an unexplored feature of this important molecule. Using recombinant technology we can can start to understand the phenomenon of the inflammatory processes involved in the degradation of the cartilage. 550Purpose: Bardet-Biedl Syndrome (BBS) is a pleiotropic disorder resulting in retinal degeneration, obesity, intellectual disability, and polydactyly. Data indicate that BBS is also associated with osteoarthritis (OA). This makes BBS mouse models useful for studying the role of primary cilia as they pertain to OA. Certain proinflammatory cytokines are known to be up-regulated through the Receptor for Advanced Glycation End Product (RAGE) pathway during the onset and progression of OA. We hypothesized that dysfunctional chondrocyte primary cilia result in OA through the up-regulation of this pathway. Methods: We performed immunohistochemistry to evaluate the level of Htra1 and TGF-b1, cellularity and histology in BBS mutant and wild type mice of various ages. Results: We observed a significant increase in HTRA1 and decrease in TGF-B1 expression in BBS mice when compared to age matched controls. Interestingly, there was no difference in OARSI scoring between BBS mutant and wild type mice. Conclusions: These data indicate that the RAGE pathway is integral to all OA cases, and that the expression of specific RAGE-related biomarkers precede cartilage degradation in the cilia disorder, BBS. These findings also provide support of the novel idea that primary cilia are an integral part of the RAGE pathway.Purpose: In previous s...

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