2. Academic Validation
  3. LPS induces fibroblast-like synoviocytes RSC-364 cells to pyroptosis through NF-κB mediated dual signalling pathway

LPS induces fibroblast-like synoviocytes RSC-364 cells to pyroptosis through NF-κB mediated dual signalling pathway

  • J Mol Histol. 2021 Aug;52(4):661-669. doi: 10.1007/s10735-021-09988-8.
Panpan Yang 1,  Wei Feng 2,  Congshan Li 1,  Yuying Kou 1,  Dongfang Li 1,  Shanshan Liu 1,  Tomoka Hasegawa 3,  Minqi Li 4
Affiliations

Affiliations

  • 1 Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Shandong University, Wenhua West Road 44-1, Jinan, 250012, China.
  • 2 Department of Endodontics, Jinan Stomatological Hospital, Jinan, 250001, China.
  • 3 Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586, Japan.
  • 4 Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Shandong University, Wenhua West Road 44-1, Jinan, 250012, China. liminqi@sdu.edu.cn.
PMID: 34085178 DOI: 10.1007/s10735-021-09988-8
Abstract

Rheumatoid arthritis (RA) is a chronic, progressive, and systemic inflammatory joint disease characterized by synovial inflammation and joint damage. Abnormal activation of fibroblast-like synoviocytes is an initial event of synovial inflammation and joint damage, which can significantly aggravate the progression of RA. Clinical studies have shown that synovitis may be associated with Pyroptosis. Therefore, this study is mainly aim for exploring the underlying mechanisms of relationship between inflammation and Pyroptosis during synovitis. A cell model of synovitis was constructed by stimulating synovial fibroblasts RSC-364 cells with lipopolysaccharide (LPS). In vitro, we found that LPS can induce Pyroptosis of synovial fibroblasts through NOD-like Receptor pyrin domain-3/Caspase-1/gasdermin D and Caspase-3/gasdermin E two signaling pathways, and these two signaling pathways can promote each Other. In addition, NF-κB signaling pathway, as the upstream of these two pathways, is involved in regulating the Pyroptosis of synovial fibroblast. These results suggest that Pyroptosis may be triggered during the occurrence of RA. We hope to provide a new perspective for the study of RA and a new therapeutic target for clinical treatment of RA.

Keywords

GSDMD; GSDME; NF-κB signal pathway; Rheumatoid arthritis (RA); pyroptosis.

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