Objective: Our previous studies revealed that normal synovial exosomes promoted chondrogenesis, and microRNA (miR)-19b-3p independently related to osteoarthritis (OA) risk. Subsequently, this study intended to further explore the effect of OA fibroblast-like synoviocyte (OA-FLS) exosomal miR-19b-3p on OA ferroptosis and its potential mechanisms.Methods: Interleukin (IL)-1β-stimulated chondrocytes and medial meniscus surgery were used to construct the OA cellular model and the OA rat model, respectively. OA-FLS exosomes with/without miR-19b-3p modification were added to the IL-1β-stimulated chondrocytes and OA rat models, followed by direct miR-19b-3p mimic/inhibitor transfection with/without SLC7A11 overexpression plasmids. miR-19b-3p, ferroptosis-related markers (malondialdehyde (MDA), glutathione (GSH)/oxidized glutathione (GSSG), ferrous ion (Fe²⁺), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long-chain family member 4 (ACSL4)), mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels were detected.Results: Enhanced ferroptosis reflected by dysregulated ferroptosis-related markers, a reduced MMP, and an increased ROS was observed in cartilage tissues from OA patients vs. controls, IL-1β-stimulated chondrocytes vs. normal ones, and OA rat models vs. sham, so did miR-19b-3p. OA-FLS exosomes promoted MDA, Fe²⁺, ACSL4, and ROS but reduced cell viability, GSH/GSSG, GPX4, SLC7A11, and MMP in IL-1β-stimulated chondrocytes, whose effect was enhanced by miR-19b-3p mimics and attenuated by miR-19b-3p inhibitors. miR-19b-3p negatively regulated SLC7A11 and directly bound to SLC7A11 via luciferase reporter gene assay. Furthermore, SLC7A11 overexpression weakened miR-19b-3p mimics’ effect on ferroptosis-related markers, MMP, or ROS in IL-1β-stimulated chondrocytes. OA-FLS exosomes also induced cartilage damage and ferroptosis in OA rats whose influence was tempered by miR-19b-3p inhibitors.Conclusion: OA-FLS exosomal miR-19b-3p enhances cartilage ferroptosis and damage by sponging SLC7A11 in OA, indicating a potential linkage among synovium, cartilage, and ferroptosis during the OA process.

Ras homolog gene family member A (RhoA) plays a major role in the Wnt/planar cell polarity (PCP) pathway, which is significantly activated in patients with rheumatoid arthritis (RA). The function of RhoA in RA synovitis and bone erosion is still elusive. Here, we not only explored the impact of RhoA on the proliferation and invasion of RA fibroblast-like synoviocytes (FLSs) but also elucidated its effect on mouse osteoclast and a mouse model of collagen-induced arthritis (CIA). Results showed that RhoA was overexpressed in RA and CIA synovial tissues. Lentivirus-mediated silencing of RhoA increased apoptosis, attenuated invasion, and dramatically upregulated osteoprotegerin/receptor activator of nuclear factor-κB ligand (OPG/RANKL) ratio in RA-FLSs. Additionally, the silencing of RhoA inhibited mouse osteoclast differentiation in vitro and alleviated synovial hyperplasia and bone erosion in the CIA mouse model. These effects in RA-FLSs and osteoclasts were all regulated by RhoA/Rho-associated protein kinase 2 (ROCK2) and might interact with Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways.