chrysin and Osteoarthritis

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.

Topics: Apoptosis; Cell Line; Chondrocytes; Collagenases; Flavonoids; HMGB1 Protein; Humans; Inflammation; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Matrix Metalloproteinase 13; Osteoarthritis; Protective Agents; Signal Transduction

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. Chrysin, a natural flavonoid extracted from honey and propolis, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effects of chrysin on OA have not been reported. This study aimed to assess the effects of chrysin on human OA chondrocytes. Human OA chondrocytes were pretreated with chrysin (1, 5, 10 μM) for 2 h and subsequently stimulated with IL-1β for 24 h. Production of NO, PGE2, MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 was evaluated by the Griess reaction and ELISAs. The messenger RNA (mRNA) expression of COX-2, iNOS, MMP-1, MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, aggrecan, and collagen-II was measured by real-time PCR. The protein expression of COX-2, iNOS, p65, p-p65, IκB-α, and p-IκB-α was detected by Western blot. The protein expression of collagen-II and p65 nuclear translocation was evaluated by immunofluorescence. We found that chrysin significantly inhibited the IL-1β-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5; and degradation of aggrecan and collagen-II. Furthermore, chrysin dramatically blocked IL-1β-stimulated IκB-α degradation and NF-κB activation. Taken together, these results suggest that chrysin may be a potential agent in the treatment of OA.

Topics: Aggrecans; Anti-Inflammatory Agents; Cells, Cultured; Chondrocytes; Collagen Type II; Flavonoids; Humans; Inflammation Mediators; Interleukin-1beta; NF-kappa B; NF-KappaB Inhibitor alpha; Osteoarthritis