AB0030 BETA BOSWELLIC ACID BLOCKS INNATE IMMUNE RESPONSES IN MULTIPLE OA JOINT CELLS

Background: Osteoarthritis (OA) incidence has skyrocketed in the last decade and yet a definitive treatment still to be found. This worldwide disease is depriving our society from their life quality become grave economic burden. Research on anti-inflammatory tools been done traditional Asian medicine. Boswellic acid plant-derived molecule Boswellia species that shown prevent cartilage loss an OA mouse model[1]. However, specific mechanism of action unclear. The activation innate immune receptors, such Toll-like receptor 4 (TLR4) involved chondrocyte-mediated inflammatory responses development. Although, boswellic inhibitory effect TLR4-mediated little known about its role chondrocyte catabolic responses. Objectives: Determine ability beta (BBA) block chondrocytes synoviocytes. Methods: In silico binding affinity TLR4 complex signalling was determined by optimized docking algorithm BIO-HPC Group facilities. vitro Cellular proteome secretome profiling (LC-MALDI/TOFF) used study pathways induced agonist (LPS [100ng/ml]) IL1R (IL1β [0.1ng/ml]). BBA RT-PCR, Western Blot ELISA primary human (hOC), murine ATDC5 chondrocytes, synoviocytes (SW982) osteoblasts (hOB). Cell viability tested using methyl-thiazolyl-tetrazolium (MTT) reagent. Nitric oxide production cell culture media assessed Griess reaction. Green Malachite Assay semi-quantify whole phosphoproteome. Ethics approved CEIC (CAEIG 2014/310). Results: validated LPS IL1β ligands revealed enrichment (NF-Kβ, NLRP3, MMPs, Interleukins, etc). Non-toxic doses [0.5-1000nM] prevented multiple articular joint cells inhibited & IL1R-dependant at mRNA protein level as factors IL6, NOS2, COX2, LCN2, MMP1, -3, -9, -13 ADAMTS4, among others. Furthermore, NF-Kβ/IKBα NLRP3/PYCARD/IL1β axis were also severely after treatment. Moreover, these results analysis showed interacted with TLR4/NF-Kβ. Conclusion: We prove inhibit -dependent (Figure 1). show NF-Kβ NLRP3 signalling, both associated OA, are blocked (mRNA protein) Our data support previous studies showing prevention animal models might come signalling. clinical practice rheumatologists, Serrata could useful nutraceutical manage inflammation due content BBA. Figure 1. References: [1]Wang, Q.; Pan, X.; Wong, H.H.; Wagner, C.A.; Lahey, L.J.; Robinson, W.H.; Sokolove, J. Oral topical attenuates osteoarthritis. Osteoarthr. Cartil. 2014 , 22 128–132, doi:10.1016/j.joca.2013.10.012. Acknowledgements: Eloi Franco-Trepat Ana Lois-Iglesias contributed equally this work. research funded non-profit FER (Fundación Española de Reumatologia /Spanish Foundation Rheumatology) through project “Búsqueda nuevos fármacos bloqueantes la inflamación asociada en condrocitos humanos artrósicos”. Disclosure Interests: None declared