Abstract
Sodium 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.Primary 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.After 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).SF 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.
Highlights
We read with great interest the research article by Qin and colleagues, in which they addressed, on the basis of their previous work, the underlying mechanisms for the protective effect of a small component of traditional Chinese herbs, sodium ferulate (SF), on osteoarthritis (OA) [1]
The caspase cascade signaling pathway only represents the extrinsic pathways of apoptotic signaling [2]
Despite the authors addressing the caspase-8 and caspase-3 pathway, they might have neglected the intrinsic apoptotic pathway characterized by the Bcl-2 family
Summary
We read with great interest the research article by Qin and colleagues, in which they addressed, on the basis of their previous work, the underlying mechanisms for the protective effect of a small component of traditional Chinese herbs, sodium ferulate (SF), on osteoarthritis (OA) [1]. The caspase cascade signaling pathway only represents the extrinsic pathways of apoptotic signaling [2]. It is well established that there are mainly two types of apoptotic signaling pathways: the aforementioned extrinsic pathway, and the intrinsic pathway originating from the mitochondria and involving activation of the Bcl-2 family [3].
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