%0 Journal Article
%T The role of the JAK/STAT signal pathway in rheumatoid arthritis
%A Charles J. Malemud
%J Archive of "Therapeutic Advances in Musculoskeletal Disease".
%D 2018
%R 10.1177/1759720X18776224
%X Proinflammatory cytokine activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal transduction pathway is a critical event in the pathogenesis and progression of rheumatoid arthritis. Under normal conditions, JAK/STAT signaling reflects the influence of negative regulators of JAK/STAT, exemplified by the suppressor of cytokine signaling and protein inhibitor of activated STAT. However, in rheumatoid arthritis (RA) both of these regulators are dysfunctional. Thus, continuous activation of JAK/STAT signaling in RA synovial joints results in the elevated level of matrix metalloproteinase gene expression, increased frequency of apoptotic chondrocytes and most prominently ¡®apoptosis resistance¡¯ in the inflamed synovial tissue. Tofacitinib, a JAK small molecule inhibitor, with selectivity for JAK2/JAK3 was approved by the United States Food and Drug Administration (US FDA) for the therapy of RA. Importantly, tofacitinib has demonstrated significant clinical efficacy for RA in the post-US FDA-approval surveillance period. Of note, the success of tofacitinib has spurred the development of JAK1, JAK2 and other JAK3-selective small molecule inhibitors, some of which have also entered the clinical setting, whereas other JAK inhibitors are currently being evaluated in RA clinical trials
%K cytokine
%K Janus kinase
%K rheumatoid arthritis
%K signal transducers and activators of transcription
%K signal transduction
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009092/