Abstract
Osteoarthritis (OA) is a chronic degenerative disease wherein the articular cartilage exhibits inflammation and degradation. Scutellarin (SCU) is a flavonoid glycoside with a range of pharmacological activities, as shown in previous studies demonstrating its anti-inflammatory activity. How SCU impacts the progression of OA, however, has not been explored to date. Herein, we assessed the impact of SCU on murine chondrocytes in an OA model system. In in vitro assays, we measured chondrocyte expression of key OA-associated factors such as matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) via qRT-PCR and Western blotting, the expression of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were detected by qRT-PCR. Our results showed that the downregulation of MMP-13, ADAMTS-5, COX-2, and iNOS expression by SCU and the overproduction of IL-6, TNF-α, and PGE2 induced by IL-1β were all inhibited by SCU in a concentration-dependent manner. Moreover, SCU was able to reverse aggrecan and collagen II degradation and nuclear factor-κB (NF-κB) and nuclear factor erythroid-derived 2-like 2 (Nrf2) signaling pathway activation both in vivo and in vitro. We further used a destabilization of the medial meniscus (DMM) murine model of OA to explore the therapeutic benefits of SCU in vivo. Together, our findings suggest SCU to be a potentially valuable therapeutic agent useful for treating OA.
Highlights
Osteoarthritis (OA) is a progressive disease wherein the articular cartilage undergoes chronic and progressive destruction (Loeser, 2009; Khan et al, 2017)
It has been demonstrated that nuclear factor erythroid-derived 2-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway is involving in inflammation disease (Feng et al, 2018; Hu et al, 2019)
We explored the impact of SCU on chondrocyte inflammation in response to IL-1b (10 ng/ml) by treating these cells with the indicated SCU doses for 24 h before IL-1b addition
Summary
Osteoarthritis (OA) is a progressive disease wherein the articular cartilage undergoes chronic and progressive destruction (Loeser, 2009; Khan et al, 2017). A number of factors are likely to influence the structural and functional alterations that characterize OA, including oxidative stress, impaired mitochondrial activity, expression of catabolic genes, and altered chondrocyte inflammatory activity (Goldring, 2000; Loeser et al, 2012). By signaling through NF-kB, IL-1b can induce a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) expression, in addition to upregulation of matrix metalloproteinases (MMPs) that can break down cartilaginous tissue. In this context, inhibition of NF-kB activation and transcription is an effective way by which OA exerts its anti-inflammatory effect. Nrf signaling has been shown to be a key anti-inflammatory defense mechanism that enhances expression of HO-1 and inhibits NF-kB activity, which could decrease the generation of inflammatory mediators such as MMPs and PGE2 and attenuate the extracellular matrix (ECM) degradation, making this a potentially viable therapeutic target in OA (Chen et al, 2006)
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