English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

The Janus kinase (JAK)—Signal transducer and activator of transcription (STAT) pathway is one of the central signaling hubs in inflammatory, immune and cancer cells. Inhibiting the JAK-STAT pathway with JAK inhibitors (jakinibs) constitutes an important therapeutic strategy in cancer and chronic inflammatory diseases like rheumatoid arthritis (RA). FDA has approved different jakinibs for the treatment of RA, including tofacitinib, baricitinib and upadacitinib, and several jakinibs are being tested in clinical trials. Here, we reviewed published studies of jakinib effects on resolving synovial pathology in inflammatory arthritis. We discussed the results of jakinibs on structural joint damage in clinical trials and explored the effects of jakinibs across different  in vitro, ex vivo , and  in vivo  synovial experimental models. We delved rigorously into experimental designs of  in vitro  fibroblast studies, deconvoluted jakinib efficacy in synovial fibroblasts across diverse experimental conditions and discussed their translatability  in vivo . Synovial fibroblasts can readily activate the JAK-STAT signaling pathway in response to cytokine stimulation. We highlighted rather limited effects of jakinibs on the  in vitro  cultured synovial fibroblasts and inferred that direct and indirect (immune cell-dependent) actions of jakinibs are required to curb the fibroblast pathology  in vivo . These actions have not been mimicked optimally in current  in vitro  experimental designs, where inflammatory stimuli do not naturally clear out with treatment as they do  in vivo . While summarizing the broad knowledge of synovial jakinib effects, our review uniquely challenges future study designs to better mimick the jakinib actions in broader cell communities, as occurring  in vivo  in the inflamed synovium. This can deepen our understanding of collective synovial activities of jakinibs and their therapeutic limitations, thereby fostering jakinib development in arthritis.

Hi-JAKi-ng Synovial Fibroblasts in Inflammatory Arthritis With JAK Inhibitors