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Published on: March 18, 2022
Scutellarin Attenuates the IL-1β-Induced Inflammation in Mouse Chondrocytes and Prevents Osteoarthritic Progression
Zucheng Luo1,2,3, Zhichao Hu1,2,3, Yujie Bian1,2,3
1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
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.
Insights
Scutellarin (SCU) may treat osteoarthritis (OA) by reducing inflammation and cartilage degradation. This study investigated SCU
Area of Science:
- Biochemistry
- Pharmacology
- Biomedical Engineering
Background:
- Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage inflammation and breakdown.
- Scutellarin (SCU), a flavonoid glycoside, possesses known anti-inflammatory properties.
- The therapeutic potential of SCU in OA progression remains unexplored.
Purpose of the Study:
- To investigate the impact of Scutellarin (SCU) on osteoarthritis (OA) progression in a murine model.
- To evaluate SCU's effects on key molecular markers of cartilage degradation and inflammation in chondrocytes.
- To assess SCU's therapeutic efficacy in vivo using a destabilization of the medial meniscus (DMM) OA model.
Main Methods:
- In vitro analysis of murine chondrocytes using qRT-PCR and Western blotting to measure expression of MMP-13, ADAMTS-5, COX-2, iNOS, IL-6, TNF-α, and PGE2.
- In vivo assessment using a destabilization of the medial meniscus (DMM) murine model of OA.
- Evaluation of SCU's impact on aggrecan and collagen II degradation, and NF-κB and Nrf2 signaling pathways.
Main Results:
- SCU significantly inhibited the expression of OA-associated factors including MMP-13, ADAMTS-5, COX-2, and iNOS in chondrocytes.
- SCU suppressed the IL-1β-induced overproduction of IL-6, TNF-α, and PGE2 in a concentration-dependent manner.
- SCU reversed aggrecan and collagen II degradation and modulated NF-κB and Nrf2 signaling pathways in both in vitro and in vivo OA models.
Conclusions:
- Scutellarin (SCU) demonstrates significant anti-inflammatory and chondroprotective effects in OA models.
- SCU effectively inhibits key molecular pathways involved in OA pathogenesis.
- SCU shows promise as a potential therapeutic agent for treating osteoarthritis.
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