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DMY protects the knee joints of rats with collagen-induced arthritis by inhibition of NF-κB signaling and osteoclastic bone resorption

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Abstract

Collagen-induced arthritis (CIA) is a widely used animal model for studying rheumatoid arthritis (RA), which manifests serious joint dysfunction, progressive bone erosion and articular cartilage destruction. Considering that joint damage in RA is caused by systemic inflammation and dihydromyricetin (DMY), the main flavonoid of Ampelopsis Michx, possesses anti-inflammatory properties, in the present study we have investigated the potential capability of DMY to inhibit inflammation-mediated joint damage and explore the underlying mechanisms. A rat model of RA induced by CIA was administered with DMY for 5 weeks. Prior to histological analysis, the knee joints were scanned by microcomputed tomography (μCT) to detect bone damage. Articular cartilage destruction was assessed by Alcian blue and Toluidine blue staining and the pathological alteration of osteoblasts and osteoclasts in joints was evaluated by hematoxylin–eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining, respectively. The effects of DMY on osteoblast differentiation and osteoclast formation in vitro were investigated. Consistent with the in vivo results, DMY had no significant effect on osteoblast differentiation but an inhibitory effect on osteoclast formation. Furthermore, we determined that the mechanism of the DMY-suppressed osteoclast formation was blocking the phosphorylation of I-κB kinase (IKK) so as to hinder the activation of nuclear factor-κB (NF-κB). Collectively, DMY could ameliorate knee joint damage, especially in articular cartilage, which is the weight-bearing region, by inhibiting osteoclast formation through NF-κB signaling.

Graphical abstract: DMY protects the knee joints of rats with collagen-induced arthritis by inhibition of NF-κB signaling and osteoclastic bone resorption

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Article information


Submitted
16 Feb 2020
Accepted
04 Jun 2020
First published
29 Jun 2020

Food Funct., 2020, Advance Article
Article type
Paper

DMY protects the knee joints of rats with collagen-induced arthritis by inhibition of NF-κB signaling and osteoclastic bone resorption

J. Wu, K. Fan, Q. Wang, B. Xu, Q. Cai and T. Wang, Food Funct., 2020, Advance Article , DOI: 10.1039/D0FO00396D

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