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Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
7,8-Dihydroxyflavone activates Nrf2/HO-1 signaling pathways and protects against osteoarthritis
Dawei Cai1, Wan Feng2, Jun Liu3
1Department of Orthopaedics, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
Abstract:
The aim of the present study was to investigate the effect of 7,8-dihydroxyflavone (7,8-DHF) against osteoarthritis (OA) and examine its regulatory role in the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in chondrocytes. Primary mouse chondrocytes were treated with 7,8-DHF to examine the expression of Nrf2 and downstream heme oxygenase 1 (HO-1). The surgical destabilization of the medial meniscus model was used to assess the effectiveness of 7,8-DHF in protecting the cartilage from damage, with knee cartilage harvested from mice for histological analysis. The results revealed that 7,8-DHF activated the Nrf2 signaling pathway in primary chondrocytes. Cartilage degradation in the 7,8-DHF-treated group was reduced significantly compared with that in the vehicle-treated group, according to histological evaluation. The gene expression of matrix metalloproteinase (MMP)1, MMP3, MMP13, interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were reduced in the cartilage of OA mice following 7,8-DHF treatment. Genetic and protein analyses indicated that the expression levels of HO-1 were upregulated in the cartilage of the knee with OA, and 7,8-DHF treatment further promoted the induction of HO-1. These results suggest that 7,8-DHF may serve as a potential therapeutic agent in OA.
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