E that embryonic molecular signaling pathways, and BMP signaling E that embryonic molecular signaling pathways, and BMP signaling PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25768400 in particular, are involved in the balance between tissue destruction, homeostasis and repair. Reference 1. RJ Lories, et al.: Bone morphogenetic proteins 2 and 6, expressed in arthritic synovium, are regulated by proinflammatory cytokines and differentially modulate fibroblast-like synoviocyte apoptosis. Arthritis Rheum 2003, 48:2807-2818. Acknowledgements MD and RL contributed equally to this work. RJUL is the recipient of a post-doctoral fellowship from the Fund for Scientific Research Flanders. This work was supported by research grant 0.390.03 from the Fund for Scientific Research Flanders and a Bristol-Myers-Squibb EULAR Young Investigator Award to RJUL.P119 Toll-like receptor expression in synovial fibroblasts and normal skin fibroblasts and induction of matrix metalloproteinase expression by various Toll-like receptor ligandsD Kyburz1, F Brentano1, O Schorr1, BA Michel1, RE Gay1, S Gay1 Center of Experimental Rheumatology, University Hospital, Zurich, Switzerland Arthritis Res Ther 2005, 7(Suppl 1):P119 (DOI 10.1186/ar1640) Toll-like receptors (TLRs) are pattern recognition receptors of the innate immune system. TLR2 has been demonstrated to be expressed in synovial tissue of patients with rheumatoid arthritis (RA) as well as in cultured synovial fibroblasts of patients with RA and osteoarthritis. However, it is not known whether other members of the TLR family are expressed in synovial fibroblasts. We have therefore examined the expression of TLR1 LR9 in these cells and performed stimulation experiments using specific TLR ligands. TLR and matrix metalloproteinase (MMP) mRNA expression was analysed by real-time PCR using 18S-cDNA as an internal control. A difference of five or more cycles between cDNA of the samples and non-RT control was considered to be the detection limit. While all fibroblasts expressed TLR1 LR6, the expression of TLR2 and TLR3 was significantly higher in synovial fibroblasts from patients with RA as compared with normal skin fibroblasts. TLR7, TLR8 and TLR9 mRNA did not reach the detection level. To assess the function of these TLRs, cultured synovial and skin fibroblasts were stimulated with the TLR ligands bacterial lipopeptide, poly (I:C), lipopolysaccharide and flagellin. All ligands stimulated the expression of MMP1, MMP3, MMP9 and MMP13 to a certain extent. Whereas the TLR2 ligand bacterial lipopeptide preferentially induced the expression of MMP1 and MMP3, the TLR3 ligand poly (I:C) was a more efficient CV205-502 hydrochloride manufacturer inducer of MMP13 and MMP3 and also induced MMP1 to a lesser extent. Normal skin fibroblasts expressed significantly lower levels of MMP3 and MMP13 mRNA as compared with synovial fibroblasts of patients with RA. Our data extend previous reports on the expression of TLRs on synovial fibroblasts to include TLR1 LR6 and document that these TLRs are functional. Depending on the TLR ligand used, MMP expression is differentially induced. This supports the notion that activation of TLR signalling pathways might contribute to joint inflammation and PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28212752 destruction in RA.P118 Noggin haploinsufficiency influences severity of arthritis in different mouse modelsM Daans, RJU Lories, I Derese, P Tylzanowski, FP Luyten Laboratory for Skeletal Development and Joint Disorders, Department of Rheumatology, University Hospitals Leuven, Katholieke Universiteit Leuven, Belgium Arthritis Res Ther 2005, 7(Suppl 1):P118 (DOI 10.1186/ar1639) Introduction The severity.