Advances of the small molecule drugs regulating fibroblast-like synovial proliferation for rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a type of chronic autoimmune and inflammatory disease. In the pathological process of RA, the alteration of fibroblast-like synoviocyte (FLS) and its related factors is the main influence in the clinic and fundamental research. In RA, FLS exhibits a uniquely aggressive phenotype, leading to synovial hyperplasia, destruction of the cartilage and bone, and a pro-inflammatory environment in the synovial tissue for perpetuation and progression. Evidently, it is a highly promising way to target the pathological function of FLS for new anti-RA drugs. Based on this, we summed up the pathological mechanism of RA-FLS and reviewed the recent progress of small molecule drugs, including the synthetic small molecule compounds and natural products targeting RA-FLS. In the end, there were some views for further action. Compared with MAPK and NF-κB signaling pathways, the JAK/STAT signaling pathway has great potential for research as targets. A small number of synthetic small molecule compounds have entered the clinic to treat RA and are often used in combination with other drugs. Meanwhile, most natural products are currently in the experimental stage, not the clinical trial stage, such as triptolide. There is an urgent need to unremittingly develop new agents for RA.

Current situation and trend of non-coding RNA in rheumatoid arthritis: a review and bibliometric analysis

“…Consequently, these cytokines recruit additional immune cells from the immune system and activate the NF-κB factor, resulting in the initiation of an inflammatory loop ( 134 – 136 ). Furthermore, NF-κB also participates in the regulation of Cyclin D1, Matrix Metalloproteinases (MMPs), and Vascular Endothelial Growth Factor (VEGF), which contribute to the proliferation, migration, and invasion of FLS, as well as cartilage tissue damage ( 137 – 139 ).…”

The role of YAP/TAZ on joint and arthritis

“…The typical features of RA are synovial inflammation and the concomitant destruction of adjacent cartilage and bone, and evidence is accumulating that FLSs play a pivotal role in this process. 34,76,158,159 FLSs are one of the primary pathological cell types within the RA joint, which acquire an aggressive phenotype and promote inflammation when RA progresses. 74,80,160 Still, the mechanisms involved in RA-FLS phenotype alteration remain to be elucidated.…”

The efficacy and safety of short-term and low-dose IL-2 combined with tocilizumab to treat rheumatoid arthritis

“…The high incidence, teratogenicity, disability, and poor prognosis associated with RA present significant challenges and demand effective management strategies ( 2 , 3 ). Currently, the clinical treatment of RA relies heavily on glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and disease-modifying anti-rheumatic drugs (DMARDs) such as synthetic or biologic agents ( 4 , 5 ). While these medications play a crucial role in alleviating joint symptoms and halting disease progression, they often come with potential side effects including nausea, anorexia, and bone marrow suppression due to individual variations ( 4 , 5 ).…”

“…Currently, the clinical treatment of RA relies heavily on glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and disease-modifying anti-rheumatic drugs (DMARDs) such as synthetic or biologic agents ( 4 , 5 ). While these medications play a crucial role in alleviating joint symptoms and halting disease progression, they often come with potential side effects including nausea, anorexia, and bone marrow suppression due to individual variations ( 4 , 5 ). As the need for new anti-RA therapies becomes increasingly urgent, both clinical and basic research efforts are continuously being conducted to better understand the pathogenesis of this complex disease.…”