Cinnamic Aldehyde Inhibits Lipopolysaccharide-Induced Chondrocyte Inflammation and Reduces Cartilage Degeneration by Blocking the Nuclear Factor-Kappa B Signaling Pathway.

Pu Chen,Xiaozhe Zhang,Jun Zhou,Qingfu Wang,Anmin Ruan,Yufeng Ma,Liuwei Huang

doi:10.3389/fphar.2020.00949

Abstract

Osteoarthritis (OA), as one of the top 10 causes of physical disability, is characterized by inflammation of the synovial membrane and progressive destruction of the articular cartilage. Cinnamic aldehyde (CA), an α,β-unsaturated aldehyde extracted from the traditional Chinese herbal medicine cinnamon (Cinnamomum verum J.Presl), has been reported to have anti-inflammatory, antioxidant, and anticancer properties. However, the anti-inflammatory effect of CA on OA remains unclear. The purpose of the present study was to investigate the effects of CA on inflammation, and cartilage degeneration in OA. A CCK-8 assay was performed to assess the potential toxicity of CA on cultured human OA chondrocytes. Following treatment with lipopolysaccharide (LPS) and CA, the expression of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alfa (TNF-α), was evaluated using quantitative real-time polymerase chain reaction (RT-qPCR) analysis, enzyme-linked immunosorbent assay, and Western blotting (WB). The production of matrix metalloproteinase-13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5) was also examined using RT-qPCR and WB. Furthermore, to investigate the potential anti-inflammatory mechanism of CA, biomarkers of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway (p65, IKB-α) were detected using WB. The results demonstrated that CA significantly inhibited the expressions of IL-1β, IL-6, TNF-α, MMP-13, and ADAMTS-5 in LPS-induced OA chondrocytes. CA dramatically suppressed LPS-stimulated NF-κB activation. Collectively, these results suggest that CA treatment may effectively prevent OA.

Highlights

Knee osteoarthritis (KOA), one of the most common degenerative musculoskeletal diseases involving chronic pain and dysfunction (Felson et al, 2000), is characterized by inflammation of the synovial membrane and progressive destruction of the articular cartilage (Berenbaum, 2013; Malemud, 2015)
IL-1b can induce the synthesis of inducible nitric oxide synthase and stimulate the production of nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and tumor necrosis factor- alpha (TNFa) (Goldring and Goldring, 2004; Bianchi et al, 2005; Wang et al, 2011; Fioravanti et al, 2012), which is associated with OA progression
IL-1b can stimulate the release of matrix metalloproteinases (MMPs) and a disintegrin and MMP with thrombospondin motifs (ADAMTS) (Santangelo et al, 2012); MMPs and ADAMTS can significantly promote the degradation of extracellular matrix (ECM), which further aggravates the progression of OA

Summary

Introduction

Knee osteoarthritis (KOA), one of the most common degenerative musculoskeletal diseases involving chronic pain and dysfunction (Felson et al, 2000), is characterized by inflammation of the synovial membrane and progressive destruction of the articular cartilage (Berenbaum, 2013; Malemud, 2015). Cartilage damage has been reported to induce synovial inflammation (Scotece et al, 2018), and chondrocyte‐mediated inflammatory responses play a key role in the development and progression of osteoarthritis (OA) (Konttinen et al, 2012). Effective inhibition of chondrocyte inflammation may play a role in reversing or altering the progression of OA. Many signaling pathways play a crucial role in the development and progression of OA. Activated NF-kB can induce excessive expressions of interleukin (IL)-1b and matrix metalloproteinases (MMPs), which play key roles in inflammation and extracellular matrix (ECM) degradation (Santangelo et al, 2012; Kepczynska et al, 2017). IL-1b can stimulate the release of MMPs and a disintegrin and MMP with thrombospondin motifs (ADAMTS) (Santangelo et al, 2012); MMPs and ADAMTS can significantly promote the degradation of ECM, which further aggravates the progression of OA

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