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

and colleagues, in which they addressed, on the basis of their previous work, the underlying mechanisms for the protective eff ect of a small component of traditional Chinese herbs, sodium ferulate (SF), on osteoarthritis (OA) [1]. Utilizing the classical in vitro OA chondrocyte model induced by IL-1β, they provided lines of evidence that SF does make a big diff erence to the OA model in a dose-dependent manner. Furthermore, the underlying mechanisms of the eff ects were owing to the regulative role of SF on the apoptotic machinery. However, we would like to supple ment as well as applaud the authors' fi ndings with particular reference to the apoptotic machinery regu lation. First, the caspase cascade signaling pathway only represents the extrinsic pathways of apoptotic signaling [2]. In fact, it is well established that there are mainly two types of apoptotic signaling pathways: the afore mentioned extrinsic pathway, and the intrinsic pathway originating from the mitochondria and involving activation of the Bcl-2 family [3]. Both the extrinsic and intrinsic pathways play important roles in the apoptosis of human OA as well as the chondrocyte-like cells, nucleus pulposus cells [4]. 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. Th e integration of the entire apop-totic pathways might strengthen the basis of the conclusion they drew. Second, the authors might have omitted one important regulatory molecular family; that is, miRNAs. Indeed, there is accumulating evidence demonstrating that miRNAs play critical regulatory roles in a variety of physiological and pathological processes, including cell growth, migration and apoptosis [5,6]. Specifi cally, the apoptotic machinery and infl ammation process are regulated by miRNAs. Wang and colleagues noted that miR-155 targets FADD and CASP3 as the underlying mechanisms for the increase of apoptosis in human disc degeneration [7]. Given that nucleus pulposus cells are similar to chondrocytes in histology and cell markers, we might reasonably deduce that miRNAs could play roles in apoptosis in OA. At this point, SF might exert its infl uence by altering the expression of miRNAs. Such a benefi cial investigation is promising with the hope of providing novel insights into the molecular mechanisms for the eff ects of SF on OA. Th ird, the authors claimed that diff erent concentrations of SF have no eff ect on normal chondrocyte viability in the fi rst section of Results. …