Clusterin exacerbates interleukin-1β-induced inflammation via suppressing PI3K/Akt pathway in human fibroblast-like synoviocytes of knee osteoarthritis
Issued Date
2022-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85132078822
Pubmed ID
35705674
Journal Title
Scientific Reports
Volume
12
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.12 No.1 (2022)
Suggested Citation
Ungsudechachai T., Honsawek S., Jittikoon J., Udomsinprasert W. Clusterin exacerbates interleukin-1β-induced inflammation via suppressing PI3K/Akt pathway in human fibroblast-like synoviocytes of knee osteoarthritis. Scientific Reports Vol.12 No.1 (2022). doi:10.1038/s41598-022-14295-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86410
Title
Clusterin exacerbates interleukin-1β-induced inflammation via suppressing PI3K/Akt pathway in human fibroblast-like synoviocytes of knee osteoarthritis
Author's Affiliation
Other Contributor(s)
Abstract
This study aimed to examine, a multifaceted chaperon-like protein exerting anti-inflammatory action, clusterin (CLU), mRNA and protein levels in the systemic and local joint environment of knee osteoarthritis (OA) patients and to determine whether CLU inhibited interleukin (IL)-1β-induced inflammation in knee OA fibroblast-like synoviocytes (FLSs) through modulating phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. CLU protein and mRNA expressions in the synovium and its protein levels in plasma and synovial fluid of knee OA patients were measured using immunohistochemistry, real-time PCR, and ELISA, respectively. Anti-inflammatory effect of CLU was further elucidated in knee OA FLSs treated with IL-1β in the absence or presence of CLU, CLU alone, or PI3K inhibitor (LY294002) along with IL-1β and CLU. In a clinical study, compared with knee OA patients without synovitis, CLU protein and mRNA were expressed in the synovium of knee OA patients with synovitis, especially those with high-grade, consistent with analyses of its plasma and synovial fluid levels. CLU mRNA and protein levels were both associated with synovitis severity. An in vitro study uncovered that CLU significantly alleviated IL-1β-induced overproduction of nitric oxide and IL-6 in knee OA FLSs. Furthermore, CLU significantly attenuated inflammation and extracellular matrix degradation induced by IL-1β via down-regulating expressions of IL-6, nuclear factor kappa B, and matrix metalloproteinase-13. Mechanistically, CLU significantly impeded IL-1β-induced Akt phosphorylation in knee OA FLSs, in line with addition of LY294002 along with IL-1β and CLU. These findings suggest that CLU may have potential as a novel therapeutic target for synovitis and cartilage destruction in knee OA.