TREM1 Inhibits Autophagy and Promotes Apoptosis to Aggravate Osteoarthritis

Abstract

Objectives: This study aimed to explore the effect and possible mechanisms of triggering receptor expressed on myeloid cells 1 (TREM1) on osteoarthritis (OA). Methods: An in vivo OA rat model was used, which was mediated by injecting 4% papain mixed with 0.3 mol/L L-cysteine. An in vitro study of OA chondrocytes was also conducted, which was induced by interleukin (IL)-1β treatment. Immunofluorescence staining was used to identify isolated chondrocytes. Hematoxylin-eosin (HE) staining and toluidine blue (TB) staining were adopted for evaluating the pathological injury of rats articular cartilage tissue. The enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), western blot, cell counting kit-8 (CCK-8) and flow cytometry experiments were performed to evaluate the effects of TREM1 in OA progression in vivo and in vitro. Chondrocyte autophagy was observed by transmission electron microscopy (TEM). Results: The OA model group exhibited severe histopathological damage, high serum tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) levels, and decreased cell autophagy (downregulated autophagy-related gene 5 (ATG5), light chain 3 (LC3)-II and Beclin-1) in rat knee cartilage tissues. TREM1 was markedly overexpressed in OA samples. Transfection with si-TREM1 to knock down TREM1 significantly alleviated OA rats histopathologic damage in articular cartilage, inhibited pro-inflammatory IL-6 and tumor necrosis factor α (TNF-α) levels, promoted autophagy, and increased IL-1β-induced chondrocyte activity and autophagy, and decreased cell apoptosis rate. Overexpression of TREM1 in chondrocytes induced by IL-1β presented the opposite effect. In addition, the knockdown of TREM1 was proved to suppress nuclear factor-κB (NF-κB) p65 expression in vivo and in vitro. Conclusions: TREM1 aggravates OA progression by inhibiting cell autophagy and promoting cell apoptosis and inflammation. This suggests that TREM1 could be a potential target for treating osteoarthritis.