TRIM38 protects chondrocytes from IL-1β-induced apoptosis and degeneration via negatively modulating nuclear factor (NF)-κB signaling

Abstract

Tripartite motif protein 38 (TRIM38) has been documented as a vital modulator of inflammation. However, the relevance of TRIM38 in osteoarthritis is not yet known. In this work, we aimed to explore any possible effects of TRIM38 on interleukin-1β (IL-1β)-stimulated chondrocytes, an in vitro cellular model of osteoarthritis. Analyzing our data showed significant decreases in the levels of TRIM38 in chondrocytes following IL-1β stimulation. Gain-of-function studies revealed that overexpression of TRIM38 markedly increased the viability of IL-1β-stimulated chondrocytes while decreasing their rate of apoptosis and degeneration. Conversely, depletion of TRIM38 enhanced the sensitivity of chondrocytes to IL-1β-induced injury. Further research demonstrated that TRIM38 was capable of inhibiting IL-1β-induced activation of nuclear factor (NF)-κB signaling. Reactivation of NF-κB markedly reversed TRIM38-overexpression-mediated effects, while inhibition of NF-κB significantly abolished TRIM38-depletion-induced effects in IL-1β-stimulated chondrocytes. In summary, the findings of this work suggest that TRIM38 is capable of ameliorating IL-1β-induced apoptosis and degeneration of chondrocytes via suppression of NF-κB signaling. Our work indicates a potential role of TRIM38 in osteoarthritis and proposes it as a new therapeutic target for osteoarthritis.