1. Academic Validation
  2. Daphnoretin relieves IL-1β-mediated chondrocytes apoptosis via repressing endoplasmic reticulum stress and NLRP3 inflammasome

Daphnoretin relieves IL-1β-mediated chondrocytes apoptosis via repressing endoplasmic reticulum stress and NLRP3 inflammasome

  • J Orthop Surg Res. 2022 Nov 16;17(1):487. doi: 10.1186/s13018-022-03316-w.
Jianbo Zhou 1 Qinzhi Wang 2
Affiliations

Affiliations

  • 1 Department of Orthopedics, Xingshan People's Hospital, Yichang, 443000, Hubei, China.
  • 2 Department of Orthopaedics, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, No. 141, Tianjin Road, Huangshi, 435000, Hubei, China. wzb15071166208@163.com.
Abstract

Background: Osteoarthritis (OA), mainly caused by severe joint degeneration, is often accompanied by joint pain and dysfunction syndrome. Inflammatory mediators and Apoptosis play key roles in the evolution of OA. It is reported that daphnoretin has significant Antiviral and anti-tumor values. The present study aims at investigating the role of daphnoretin in OA.

Methods: The OA mouse model was constructed by performing the destabilization of the medial meniscus through surgery, and the OA cell model was induced in ATDC5 chondrocytes with IL-1β (10 ng/mL) in vitro. Chondrocyte viability and Apoptosis were measured by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), Caspase-3 activity, and flow cytometry. The levels of COX-2, iNOS, TNF-α, IL-6, Bax, Bcl2, cleaved-Caspase3, endoplasmic reticulum stress (ERS) proteins (GRP78, CHOP, ATF6, and Caspase-12), and NLRP3-ASC-Caspase1 inflammasome were determined by quantitative Real-Time PCR or western blot. The concentrations of TNF-α, IL-6, and PGE2 were tested by enzyme-linked immunosorbent assay. The content of nitrates was detected by the Griess method. In vivo, morphologic differences in knee joint sections and the thickness of the subchondral bone density plate in mice were observed by hematoxylin-eosin (H&E) staining and safranin O-fast green staining.

Results: Daphnoretin effectively choked IL-1β-induced chondrocyte Apoptosis and facilitated cell viability. Daphnoretin dose-dependently abated ERS, inflammatory mediators, and the activation of NLRP3 inflammasomes in IL-1β-induced chondrocytes. What's more, in vivo experiments confirmed that daphnoretin alleviated OA progression in a murine OA model by mitigating inflammation and ERS.

Conclusion: Daphnoretin alleviated IL-1β-induced chondrocyte Apoptosis by hindering ERS and NLRP3 inflammasome.

Keywords

Daphnoretin; Endoplasmic reticulum stress; NLRP3; Osteoarthritis.

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