Shaojian Chen1, Zhihuan Luo1, Xiaguang Chen1. 1. Department of Sports Medical, Ganzhou People's Hospital & the Affiliated Ganzhou Hospital of Nanchang University, Jiangxi Province, China.
Abstract
BACKGROUND: As a potential anti-arthritic agent, Andrographolide (And) is capable of promoting chondrocyte proliferation and preventing apoptosis in pathologic condition. The present study aimed to explore the roles of And in in vivo and in vitro models of osteoarthritis (OA), as well as its underlying molecular mechanisms. METHODS: An OA mouse model was established using anterior cruciate ligament transection operation on the left knee joint. The pathological changes of articular cartilage were assessed using safranin O staining. Chondrocyte proliferation and apoptosis were measured using cell a counting kit-8 assay and flow cytometry. Bioinformatics algorithms and a luciferase reporter assay were used to evaluate matrix metalloproteinase13 (MMP13) as a direct target of miR-27-3p. RESULTS: And had the ability to prevent catabolism and facilitate anabolism of articular cartilage in an experimental OA model in mice. In addition, And alleviated chondrocyte apoptosis in in vitro and in vivo models of OA. We also found that both up-regulation of MMP13 and down-regulation of miR-27-3p in the proximal tibia of OA mice and interleukin (IL)-1β-stimulated chondrocytes were reversed by And administration simultaneously. MMP13 was validated as direct target of miR-27-3p and could be suppressed by overexpression of miR-27-3p in mouse chondrocyte. Furthermore, overexpression of miR-27-3p or MMP13 loss-of-function in chondrocytes could alleviate IL-1β-induced apoptosis. CONCLUSIONS: These results indicated that miR-27-3p/MMP13 signaling axis might be a potential therapeutic target of And for preventing the progression of OA.
BACKGROUND: As a potential anti-arthritic agent, Andrographolide (And) is capable of promoting chondrocyte proliferation and preventing apoptosis in pathologic condition. The present study aimed to explore the roles of And in in vivo and in vitro models of osteoarthritis (OA), as well as its underlying molecular mechanisms. METHODS: An OAmouse model was established using anterior cruciate ligament transection operation on the left knee joint. The pathological changes of articular cartilage were assessed using safranin O staining. Chondrocyte proliferation and apoptosis were measured using cell a counting kit-8 assay and flow cytometry. Bioinformatics algorithms and a luciferase reporter assay were used to evaluate matrix metalloproteinase13 (MMP13) as a direct target of miR-27-3p. RESULTS: And had the ability to prevent catabolism and facilitate anabolism of articular cartilage in an experimental OA model in mice. In addition, And alleviated chondrocyte apoptosis in in vitro and in vivo models of OA. We also found that both up-regulation of MMP13 and down-regulation of miR-27-3p in the proximal tibia of OAmice and interleukin (IL)-1β-stimulated chondrocytes were reversed by And administration simultaneously. MMP13 was validated as direct target of miR-27-3p and could be suppressed by overexpression of miR-27-3p in mouse chondrocyte. Furthermore, overexpression of miR-27-3p or MMP13 loss-of-function in chondrocytes could alleviate IL-1β-induced apoptosis. CONCLUSIONS: These results indicated that miR-27-3p/MMP13 signaling axis might be a potential therapeutic target of And for preventing the progression of OA.
Authors: Maria-Luisa Pérez-Lozano; Annabelle Cesaro; Marija Mazor; Eric Esteve; Sabine Berteina-Raboin; Thomas M Best; Eric Lespessailles; Hechmi Toumi Journal: Antioxidants (Basel) Date: 2021-02-09