Methylene blue prevents osteoarthritis progression and relieves pain in rats via upregulation of Nrf2/PRDX1

Abstract

Oxidative stress-related cartilage degeneration, synovitis, and joint pain play vital roles in the progress of osteoarthritis (OA). Anti-oxidative stress agents not only prevent structural damage progression but also relieve OA-related pain. In this study, we investigated the therapeutic effect of methylene blue (MB), a classical and important anti-oxidant with strong neural affinity. Experimental OA was established in rats by radial transection of medial collateral ligament and medial meniscus (MCLT + MMT) of the right knee joint. The OA rats received intra-articular injection of MB (1 mg/kg) every week starting one week after surgery. We showed that MB administration exerted significant cartilage protection, synovitis inhibition as well as pain relief in OA rats. In human chondrocytes and fibroblast-like synoviocytes, MB significantly attenuated tert-butyl hydroperoxide (TBHP)-induced inflammatory response and oxidative stress. We demonstrated that these effects of MB resulted from dual targets of important antioxidant enzymes, Nrf2 and PRDX1, which also mutually reinforcing and participated in an interaction. Furthermore, we found that calcitonin gene-related peptide (CGRP), a neural inflammatory mediator, was accumulated around the vessel in synovium and subchondral bone in OA rats and in TBHP-treated primary cortical neurons; MB administration significantly inhibited CGRP expression through upregulation of Nrf2 and PRDX1. Taken together, these results suggest that MB ameliorates oxidative stress via Nrf2/PRDX1 regulation to prevent progression and relieve pain of OA.

Caffeic acid phenethyl ester attenuates osteoarthritis progression by activating NRF2/HO‑1 and inhibiting the NF‑κB signaling pathway

“…Increasing evidence has indicated that the NRF2/HO-1 signaling pathway plays a pivotal role in the protection of joint cartilage during OA pathogenesis ( 58 ). The activation of the NRF2/HO-1 signaling pathway inhibits the production of MMPs and inflammatory factors to reduce the degradation of ECM in OA chondrocytes ( 19 , 59 , 60 ). A previous study reported that CAPE exerted its anti-inflammatory effects by inducing the activation of the NRF2/HO-1 signaling pathway; CAPE attenuated 2,4,6-trinitrobenzene sulfonic acid-induced colitis via the activation of the NRF2 signaling pathway in the rat inflamed colon ( 61 ).…”

Oral administration of live combined Bacillus subtilis and Enterococcus faecium alleviates colonic oxidative stress and inflammation in osteoarthritic rats by improving fecal microbiome metabolism and enhancing the colonic barrier

“…Inflammation and oxidative stress were also present in rats. Addressing oxidative stress and inflammation is a common approach to treating OA and is currently a key research area in OA treatment (Li et al, 2022 ; Zhu et al, 2022 ). Here, we also explored the effects of probiotics on OA-induced colonic damage and found that intervention with B. subtilis and E. faecium alleviated OA-induced colonic inflammation and oxidative stress by improving fecal metabolism and enhancing the intestinal barrier.…”

Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway

“…A micro-CT scanner (mCT80, Scanco Medical AG, Wangen-Brüttisellen, Switzerland) with a current of 114 μA, a voltage of 70 kV, and a resolution of 15.6 μm per pixel, was used to analyse the microstructure of the complete knee joints, as described previously [ 21 ]. Scanco Medical software was used to acquire the reconstruction images.…”