TNF/TNFR signal transduction pathway-mediated anti-apoptosis and anti-inflammatory effects of sodium ferulate on IL-1β-induced rat osteoarthritis chondrocytes in vitro

Abstract

IntroductionSodium ferulate (SF) is a natural component of traditional Chinese herbs. Our previous study shows that SF has a protective effect on osteoarthritis (OA). The objective of this study was to investigate the effect of SF on the TNF/TNF receptor (TNFR) signal transduction pathway of rat OA chondrocytes.MethodsPrimary rat articular chondrocytes were co-treated with IL-1β and SF. Chondrocyte apoptosis was assessed by fluorescein isothiocyanate-annexin V/propidium iodide assay. The PCR array was used to screen the expression of 84 key genes involved in apoptosis. The release of TNFα and prostaglandin E2 were analyzed by ELISA. Expressions of proteins were assessed by western blotting. The activity of NF-κB was determined by electrophoretic mobility shift assay (EMSA). Gene expression of inducible nitric oxide synthase (iNOS) was evaluated by real-time quantitative PCR. The nitric oxide content was measured with the Griess method.ResultsAfter treatment with SF, the apoptosis rate of chondrocytes significantly attenuated (P < 0.01). Results of the apoptosis PCR array suggested that mRNA expression of some core proteins in the TNF/TNFR pathway showed valuable regulation. The protein expressions of TNFα, TNFR-1, TNF receptor-associated death domain, caspase-8 and caspase-3 were prevented by SF in a concentration-dependent manner. SF also inhibited activities of caspase-8 and caspase-3 compared with the OA model control (P < 0.01). TNF receptor-associated factor-2 expression, phosphorylations of inhibitor of NF-κB kinase (IKK) subunits alpha and beta, and NF-κB inhibitor, alpha (IκBα) were all concentration-dependently suppressed by SF treatment. The results of EMSA showed that SF inhibited the activity of NF-κB. In addition, the expressions of cycloxygenase-2 and iNOS and the contents of prostaglandin E2 and NO were attenuated with the treatment of SF (P < 0.01).ConclusionSF has anti-apoptosis and anti-inflammatory effects on an OA model induced by IL-1β in vitro, which were due to inhibitory actions on the caspase-dependent apoptosis pathway and the IKK/NF-κB signal transduction pathway of the TNF/TNFR pathway.

Tumor necrosis factor receptor-II nt587 polymorphism in Chinese Han patients with ankylosing spondylitis

“…Furthermore, the mutated form was reported to diminish the ability to recruit TRAF2 (the anti-apoptotic pathway). Nevertheless, it caused no alteration of the cJun N-terminal kinase activation (the apoptotic pathway), and pre-stimulation of this mutated TNFRII gene resulted in greater activation of TNFRII-mediated apoptosis compared to the wild-type form (Till et al, 2005;Qin et al, 2012).…”

Catalase Enhances Viability of Human Chondrocytes in Culture by Reducing Reactive Oxygen Species and Counteracting Tumor Necrosis Factor-α-Induced Apoptosis

“…Cell apoptosis is evoked by multiple pathways but mainly the intrinsic and extrinsic signaling cascades, both of which result in activation of executor caspases through the initiator caspase Cas-8 [51]. The association of TNF-α with TNFR [12] on the cell surface recruits TRADD, FADD to form the cytosolic platform of DISC as a ligand-dependent transmembrane signaling receptor [52] that initiates inflammation [16] and apoptosis cascade [17,18]. DISC provokes the Cas-8 to activate Cas-3, which sabotages a range of cytoplasmic proteins and dismantles chromatin and nucleoplasmic proteins in the nucleus, eventually resulting in apoptosis.…”

“…The key inflammatory cytokine TNF-α and IL-1β coexist in the process of inflammation and pathogenesis in OA [12], the presence of TNF-α in cells, which is also stimulated by IL-1β [15], initiates inflammation and apoptosis by association with the TNF receptor (TNFR) on cell surface [16], leading to the formation of death inducing signaling complex (DISC). DISC recruits the TNF receptor-associated dead domain (TRADD), Fasassociated dead domain protein (FADD) to initiate the death signaling, which triggers the activation of apoptotic enzymes of caspase-8 (Cas-8) and caspase 3 (Cas-3) [17]. Significantly activated Cas-8 directly activates Cas-3 to introduce apoptosis (the extrinsic route) rather than amplifying Cas-3 activation mediated by low levels of activated Cas-8 via mitochondria (the intrinsic route) [18].…”

Puerarin attenuates inflammation and oxidation in mice with collagen antibody-induced arthritis via TLR4/NF-κB signaling

“…Oxidation may be a pathophysiological process of OA, the disorder of antioxidant defensive system in OA patients is a critical factor of joint oxidation. Osteoarticular inflammatory diseases refer to inflammation in joints, which has a complicated pathogenesis and varying course (7). Over the last century, with the development of research in biochemistry, genetics, immunology, molecular biology and pain iconography, comprehensive studies of osteoarticular inflammatory disease have been conducted to elucidate epidemiology, etiology, clinical features, pathogenesis and differential diagnoses, and develop treatment strategies (8).…”