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

Bone & Joint Research

article

Haokun Mo¹  Zhenggang Wang¹  Zhiyi He¹  Junlai Wan¹  Rui Lu¹  Chenwen Wang²  Anmin Chen¹  Peng Cheng¹ 

[1] Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;Department of Orthopedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology

关键词: Peli1;    Chondrocyte;    Macrophage;    Polarization;    Toll-like receptor;    Osteoarthritis (OA);    chondrocytes;    macrophages;    apoptosis;    inflammation;    synovitis;    RNA;    destruction of cartilage;    interleukin;    inflammatory diseases;   

DOI  :  10.1302/2046-3758.122.BJR-2022-0214.R1

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsPellino1 (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.MethodsAfter inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (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 haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry.ResultsIn chondrocytes, knockdown of Peli1 produced anti-inflammatory and anti-apoptotic effects by targeting the TLR and NF-κB signalling pathways. We found that in macrophages, knockdown of Peli1 can inhibit M1-type polarization of macrophages. In addition, the corresponding 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 knockdown Peli1 reduces cartilage destruction and synovial inflammation.ConclusionKnockdown of Peli1 has a therapeutic effect on OA, which therefore makes it a potential therapeutic target for OA.

【 授权许可】

CC BY-NC