Dihydrocaffeic acid improves IL-1β-induced inflammation and cartilage degradation via inhibiting NF-κB and MAPK signalling pathways

Abstract

AimsOsteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism.MethodsIn vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage.ResultsDHCA prevented iNOS and IL-6 from being upregulated by IL-1β. Moreover, the IL-1β-induced upregulation of MMPs could be inhibited by DHCA. Additionally, the administration of DHCA counteracted IL-1β-induced downregulation of aggrecan, collagen II, and SOX9. DHCA protected articular cartilage by blocking the NF-κB and MAPK pathways. Furthermore, DHCA mitigated the destruction of articular cartilage in vivo.ConclusionWe present evidence that DHCA alleviates inflammation and cartilage degradation in OA chondrocytes via suppressing the NF-κB and MAPK pathways, indicating that DHCA may be a potential agent for OA treatment.Cite this article: Bone Joint Res 2023;12(4):259–273.

A Comparative Study of CFA and MIA Induction Models in Rat Knee Arthritis

“…Surprisingly, the CFA group had much higher IL-1β levels than the MIA group. 23,24 This study supports the idea that inducing MIA by directly injuring cartilage might result in a powerful inflammatory response defined by increased IL-1β production 25 . CTX-II levels, on the other hand, showed opposing tendencies.…”

HSYA prevents IL‐1β‐induced human chondrocyte damage in osteoarthritis by inhibiting NF‐κB activation

“…Chondrocytes are the sole cells present in articular cartilage and are vital for maintaining the stability of the extracellular matrix (ECM). Chondrocyte damage plays a crucial role in osteoarthritis (Lu et al., 2023; Sun et al., 2024; Xia et al., 2023). Activation of the NF‐κB signaling pathway induces the phosphorylation and degradation of IKβα in the cytoplasm, translocation of p65 to the nucleus, and disruption of ECM homeostasis in chondrocytes (Guo et al., 2021; Jun et al., 2020; Yang et al., 2022).…”

Disease-modifying agents in osteoarthritis: where are we now and what does the future hold?

“…Such agents include bone morphogenetic proteins (BMPs), 9 , 10 Wingless-like signalling inhibitors, 11 - 13 proteinase inhibitors, 14 - 17 growth factors, 18 - 20 and anabolic bone remodelling agents. 21 - 23 More recently, there has been increasing interest in novel agents and themes, including specific plant extracts, 24 the action of non-coding RNAs (ncRNAs), 25 , 26 the influence of the gut microbiome, 27 , 28 and gene-environment interactions, 29 - 31 which could be harnessed in the OA disease process.…”

“…More recently, DHCA demonstrated chondroprotective effects in vitro and in a destabilised medial meniscus OA mouse model, through downregulation of the inflammatory mediators nitric oxide synthase and IL-6. 24 …”