Carboxymethyl‑chitosan attenuates inducible nitric oxide synthase and promotes interleukin‑10 production in rat chondrocytes

Abstract

Abstract. Osteoarthritis (OA) is a common age-related degenerative joint disease, which is caused by the breakdown of joint cartilage and the underlying bone. Carboxymethyl (CM)-chitosan is a soluble derivative of chitosan that has similar physicochemical properties to the extracellular proteoglycans identified in hyaline cartilage. Previous studies have demonstrated that CM-chitosan serves a protective role in a rabbit OA model. The aim of the present study was to investigate the effect of CM-chitosan on NO production and inflammation through its upregulation of interleukin (IL)-10, and the activation of the janus kinase (JAK)/signal transducer and activator of transcription (STAT)/suppressor of cytokine signaling (SOCS) signaling pathway. In the present study primary rat chondrocytes were induced to inflammation with 2 µg/ml lipopolysaccharide. The cells were subsequently subjected to increasing concentrations of CM-chitosan (50, 100 and 200 µg/ml) and the relative mRNA and protein expression of inducible nitric oxide synthase (iNOS), IL-10, JAK1, STAT3 and SOCS3 were measured by RT-qPCR and western blot analysis respectively. The results revealed that CM-chitosan attenuated inflammation by significantly reducing iNOS expression and upregulating the anti-inflammatory cytokine IL-10 in a dose-dependent manner (P<0.05). The expression of JAK1, STAT3 and SOCS3 were also significantly upregulated by CM-chitosan (all P<0.05).

Protective Effect of Methane-Rich Saline on Acetic Acid-Induced Ulcerative Colitis via Blocking the TLR4/NF-κB/MAPK Pathway and Promoting IL-10/JAK1/STAT3-Mediated Anti-inflammatory Response

“…Lactobacillus rhamnosus GR-1 supernatant was able to increase IL-10 output and activated the JAK/STAT pathway to exert an anti-inflammatory property in lipopolysaccharide-stimulated placental trophoblast cells [34]. Carboxymethyl chitosan could attenuate inducible nitric oxide synthase and protect against osteoarthritis through the IL-10/JAK1/STAT3 pathway [35]. The expression of IL-10 could inhibit the expression of proinflammatory mediators such as cell surface receptors, chemokines, and cytokines.…”

pNNS-Conjugated Chitosan Mediated IGF-1 and miR-140 Overexpression in Articular Chondrocytes Improves Cartilage Repair

“…NO as an inflammatory mediator and catabolizing factor is closely related to the damage of cartilage, which can inhibit proteoglycan and COL2A1 synthesis and induce matrix metalloproteinase (MMP S ) synthesis in chondrocytes. High NO concentrations significantly induce chondrocyte apoptosis and decrease chondrocyte vitality [39, 40], so inhibition of NO production is a potential strategy for the treatment of cartilage damage. In this study, the outcomes showed that overexpression of IGF-1 and miR-140 inhibits NO production, inhibits apoptosis, and promoted chondrocyte against of IL-1 β antiproliferative effect, and IGF-1 and miR-140 jointly significantly enhance these effects both in vitro and in vivo .…”

Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine

“…It was also demonstrated that chondrocytes cultured in CS-alginate beads reduce the expression of inflammatory cytokines (IL-6 and IL-8) and increase cartilage matrix components (hyaluronan and aggrecan) synthesis in vitro, in comparison to alginate beads alone [86]. CS derivative carboxymethyl-CS in a dose-dependent manner reduced the inflammatory profile of primary rat chondrocytes by reducing iNOS expression and upregulating the anti-inflammatory cytokine IL-10 in vitro [87]. In another study, the addition of hyaluronic acid-CS NPs to a pellet co-culture of the human infrapatellar fat pad (IPFP)-derived mesenchymal stem cells (MSCs) with osteoarthritic chondrocytes increased chondrogenic differentiation [88].…”