Inflammation-Driven Secretion Potential Is Upregulated in Osteoarthritic Fibroblast-Like Synoviocytes

Abstract

Osteoarthritis (OA) is one of the most common joint pathologies and a major cause of disability among the population of developed countries. It manifests as a gradual degeneration of the cartilage and subchondral part of the bone, leading to joint damage. Recent studies indicate that not only the cells that make up the articular cartilage but also the synoviocytes, which build the membrane surrounding the joint, contribute to the development of OA. Therefore, the aim of the study was to determine the response to inflammatory factors of osteoarthritic synoviocytes and to identify proteins secreted by them that may influence the progression of OA. This study demonstrated that fibroblast-like synoviocytes of OA patients (FLS-OA) respond more strongly to pro-inflammatory stimulation than cells obtained from control patients (FLS). These changes were observed at the transcriptome level and subsequently confirmed by protein analysis. FLS-OA stimulated by pro-inflammatory factors [such as lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) were shown to secrete significantly more chemokines (CXCL6, CXCL10, and CXCL16) and growth factors [angiopoietin-like protein 1 (ANGPTL1), fibroblast growth factor 5 (FGF5), and insulin-like growth factor 2 (IGF2)] than control cells. Moreover, the translation of proteolytic enzymes [matrix metalloprotease 3 (MMP3), cathepsin K (CTSK), and cathepsin S (CTSS)] by FLS-OA is increased under inflammatory conditions. Our data indicate that the FLS of OA patients are functionally altered, resulting in an enhanced response to the presence of pro-inflammatory factors in the environment, manifested by the increased production of the previously mentioned proteins, which may promote further disease progression.

Evidence supported by Mendelian randomization: impact on inflammatory factors in knee osteoarthritis

“…Research indicates that synovial-like fibroblast cells (FLS) from osteoarthritis patients secrete more growth factors, including Fibroblast Growth Factor 5 (FGF5), upon exposure to pro-inflammatory stimuli ( 53 ). Clase et al propose that FGF5, as a mitogenic stimulus for mesenchymal fibroblasts, promotes the proliferation of these fibroblasts, contributing to the formation of connective tissues such as the synovium ( 54 ).…”

Mimicking the Human Articular Joint with In Vitro Model of Neurons-Synoviocytes Co-Culture

“…When the cells evenly covered the culture surface, they were stimulated with lipopolysaccharide (LPS) or interferon-gamma (IFNγ) (4 or 24 hours for mRNA sequencing or co-culture experiment respectively) and then the insert was placed into the neuronal culture. The dosage of pro-inflammatory factors - LPS and IFNγ (Gibco) was experimentally determined at 10 ng/ml for both compounds ( 11 ).…”

Research Progress on the Pathogenesis of Knee Osteoarthritis

“…KOA patients stimulated by proinflammatory factors such as lipopolysaccharide (LPS) and TNF‐αsecrete‐related chemokines (CXCL6, CXCL10 and CXCL16) and growth factors such as angiopoietin‐like protein 1(ANGPTL1), fibroblast growth factor 5 (FGF5)and insulin‐like growth factor 2 (IGF2). 64 In vitro studies have shown that human synovial fibroblasts (HFLS) can stimulate bone regeneration by activating the PI3K/AKT signaling pathway in mesenchymal stem cells, leading to the formation of osteophytes. 65 These cytokines and chemokines in the catabolic cascade amplification cartilage matrix decomposition further enhance the destruction of articular cartilage cells, causing the induction of catabolic pathways, inhibition of matrix synthesis, and promotion of apoptosis.…”