Chrysin protects human osteoarthritis chondrocytes by inhibiting inflammatory mediator expression via HMGB1 suppression

Abstract

High-mobility group box chromosomal protein (HMGB-1) contributes to osteoarthritis (OA) by modulating various oxidative, inflammatory and apoptotic signaling pathways. The effect of chrysin (CH), a natural plant flavonoid, and its functional interaction with HMGB-1, was investigated in a chondrocyte model of OA. Human chondrocytes were pre-treated with CH, and then subsequently treated with IL-1β to induce the formation of chondrocytes similar to those found in OA joints. Next, the expression level of HMGB-1 was determined by immunofluorescence and western blot analysis. Additionally, inflammatory factor expression was measured by ELISA, and cell apoptosis was analyzed with flow cytometry. To further explore the effects of CH, HMGB-1 expression was silenced following CH treatment with small interfering (si)RNA. The results demonstrated that CH inhibited cell apoptosis, dose-dependently reduced matrix metalloproteinase (MMP) 13, collagenase and IL-6 expression, and increased collagen α-1 (II) chain (COL2A1) expression in human osteoarthritis chondrocytes. These effects of CH were accompanied by decreased HMGB-1 expression. Additionally, the expression of MMP13, collagenase, IL-6 and COL2A1, as well as apoptosis, was significantly reduced by HMGB-1 siRNA. These results demonstrated that HMGB-1 is critical for the protective effect of CH on human osteoarthritis chondrocytes, including cell apoptosis and inflammatory factor inhibition, which suggests that CH may have potential therapeutic effect in treating OA by protecting human osteoarthritis chondrocytes via HMGB1 suppression.

<p>Chrysin Induced Cell Apoptosis and Inhibited Invasion Through Regulation of TET1 Expression in Gastric Cancer Cells</p>

“…14 In this study, we have investigated the anti-cancer effects of Chrysin against GC cells both in vitro and in vivo and our data suggested that Chrysin exerted significant anti-tumor capabilities including enhanced cell apoptosis, cell cycle arrest, increased cell migration, and invasion in GC cells which further supported our previous findings in melanoma 15 cells and osteoarthritis chondrocytes. 16 Recently, studies have indicated that Chrysin exhibited the ability to regulate gene expression of hTERT in breast cancer. 17 Moreover, Chrysin could regulate MMP-9 expression in GC.…”

Relationship between the pyroptosis of fibroblast‑like synoviocytes and HMGB1 secretion in knee osteoarthritis

“…Inflammatory reactions in synovial tissues are accompanied by congestion, edema, the accumulation of inflammatory mediators and the secretion of various types of proteases, ultimately resulting in abnormal cartilage metabolism (36,37). FLSs are important factors in KOA inflammation and joint destruction during the pathological progression of Koa, primarily by secreting a wide range of proinflammatory mediators, such as il-1β, il-18, TnF-α and MMPs (38). HMGB1 has been reported to serve a proinflammatory role in KOA (23,26), and HMGB1 levels in synovial fluid are closely associated with the severity of Koa (39).…”

The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation

“…HMGB1 has been previously studied in OA; it is highly expressed in the articular cartilage and synovium and plays an important role in the process of KOA (15,16). However, the specific mechanism underlying the activity of HMGB1 in KOA has not been fully elucidated.…”