Decreased Peli1 expression attenuates osteoarthritis by protecting chondrocytes and inhibiting M1-polarization of macrophages

Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. Methods After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), inter-leukin (IL)-1 beta was used to simulate inflammation, and OA-related indicators such as syn-thesis, decomposition, inflammation, and apoptosis were detected. Toll -like receptor (TLR) and nuclear factor -kappa B (NF -KB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopoly-saccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by hae-matoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochem-istry. Results In chondrocytes, knockdown of Peli1 produced anti-inflammatory and anti-apoptotic effects by targeting the TLR and NF -KB signalling pathways. We found that in macrophages, knock-down of Peli1 can inhibit M1 -type polarization of macrophages. In addition, the correspond-ing conditioned culture medium of macrophages applied to chondrocytes can also produce an anti-apoptotic effect. During in vivo experiments, the results have also shown that knock-down Peli1 reduces cartilage destruction and synovial inflammation. Conclusion Knockdown of Peli1 has a therapeutic effect on OA, which therefore makes it a potential thera-peutic target for OA.