Knockdown of TREM-1 suppresses IL-1β-induced chondrocyte injury via inhibiting the NF-κB pathway.

Triggering receptor expressed on myeloid cells 1 (TREM-1) is a recently discovered molecule that modulates inflammatory responses. This study aimed to investigate the specific function of TREM-1 in chondrocytes and its association with the pathophysiology of osteoarthritis (OA). We observed upregulation of TREM-1 in OA cartilage compared to normal tissues. Knockdown of TREM-1 suppressed interleukin 1 beta (IL-1β)-induced extracellular matrix (ECM) metabolic imbalance, pro-inflammatory cytokine production, decrease in cell viability and apoptosis. Mechanistic analyses further revealed that IL-1β-induced activation of the NF-κB pathway is suppressed upon TREM-1 knockdown, similar to the effect of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. TREM-1 expression was consistently increased in a mouse OA model in vivo, and its silencing led to inhibition of matrix metallopeptidase-13 (MMP-13) production, increased collagen type II synthesis and decreased NF-κB signaling. Our data collectively suggest that TREM-1 plays a critical in OA development through regulation of NF-κB signaling. Pharmacological inhibition of TREM-1 may therefore present an effective novel therapeutic approach for OA.