biostudies-literatureFranco-Trepat EInstituto de Salud Carlos IIIInstituto de Investigación Sanitaria de Santiago de CompostelaFundación Mutua MadrileñaMinisterio de Ciencia e InnovaciónEuropean Regional Development Fund270-286https://www.ebi.ac.uk/biostudies/studies/S-EPMC9300168biostudies-literatureUnknown179(2)<h4>Background and purpose</h4>Osteoarthritis, a major cause of disability in developed countries does not have effective treatment. Activation of TLR4 and innate immune response factors contribute to osteoarthritis progressive cartilage degradation. There are no clinically available TLR4 inhibitors. Interestingly, the antidepressant amitriptyline could block this receptor. Thus, we evaluated amitriptyline anti-TLR4 effects on human osteoarthritis chondrocytes in order to repurpose it as an inhibitor of innate immune response in joint inflammatory pathologies.<h4>Experimental approach</h4>Using in silico docking analysis, RT-PCR, siRNA, elisa, proteomics and clinical data mining of drug consumption, we explored the clinical relevance of amitriptyline blockade of TLR4-mediated innate immuneBritish journal of pharmacologyAmitriptyline blocks innate immune responses mediated by toll-like receptor 4 and IL-1 receptor: Preclinical and clinical evidence in osteoarthritis and gout.PMC9300168FECYT ‐ PRECIPITAPI14/00016FellowshipMMA 2020PI19/01446Miguel Servet IIFPU17/01706STOP ARTROSIS ‐ PR250FI20/00210PI16/01870CP15/00007PI17/00409MMA 2018Franco-Trepat ECrespo-Golmar AJorge-Mora AGomez Bahamonde RGuillan-Fresco MGualillo OPazos-Perez ABelen Bravo SLopez-Fagundez MAlonso-Perez AfalseAmitriptyline blocks innate immune responses mediated by toll-like receptor 4 and IL-1 receptor: Preclinical and clinical evidence in osteoarthritis and gout.<h4>Background and purpose</h4>Osteoarthritis, a major cause of disability in developed countries does not have effective treatment. Activation of TLR4 and innate immune response factors contribute to osteoarthritis progressive cartilage degradation. There are no clinically available TLR4 inhibitors. Interestingly, the antidepressant amitriptyline could block this receptor. Thus, we evaluated amitriptyline anti-TLR4 effects on human osteoarthritis chondrocytes in order to repurpose it as an inhibitor of innate immune response in joint inflammatory pathologies.<h4>Experimental approach</h4>Using in silico docking analysis, RT-PCR, siRNA, elisa, proteomics and clinical data mining of drug consumption, we explored the clinical relevance of amitriptyline blockade of TLR4-mediated innate immune2022-01-01T00:00:00Z2022 Jan2026-05-27T21:29:54.175Z2022-08-04T07:09:55.392ZS-EPMC93001683464394110.1111/bph.15707