基因敲除
化学
炎症
细胞凋亡
细胞生物学
小干扰RNA
巨噬细胞极化
癌症研究
分子生物学
转染
免疫学
医学
巨噬细胞
生物
体外
生物化学
基因
作者
Haokun Mo,Zhenggang Wang,Zhiyi He,Junlai Wan,Rui Lu,Chenwen Wang,Anmin Chen,Peng Cheng
出处
期刊:Bone and Joint Research
[British Editorial Society of Bone and Joint Surgery]
日期:2023-02-01
卷期号:12 (2): 121-132
标识
DOI:10.1302/2046-3758.122.bjr-2022-0214.r1
摘要
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.After 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.In 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.Knockdown of Peli1 has a therapeutic effect on OA, which therefore makes it a potential therapeutic target for OA.Cite this article: Bone Joint Res 2023;12(2):121-132.
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