Curcumin exerts a protective effect on murine knee chondrocytes treated with IL-1β through blocking the NF-κB/HIF-2α signaling pathway

Abstract

Background: Osteoarthritis (OA) is characterized by erosion and degradation of articular cartilage. This study assessed the effects of curcumin on mouse knee cartilage chondrocytes. Methods: Chondrocytes were treated for 24 hours with interleukin IL-1β (10 ng/mL) alone, or the combination of curcumin (10, 20, and 50 μM) and IL-1β. The proliferation, viability, and cytotoxicity of the chondrocytes were evaluated by the MTS assay. Expression of SOX9, AGG, Col2α, MMP9, ADAMTS5, COX2, iNOS, pIκB-α, pNF-κB, and hypoxia-inducible factor-2α (HIF-2α) were detected by western blotting or quantitative polymerase chain reaction (q-PCR). Nuclear translocation of NF-κB and HIF-2α were investigated by immunofluorescence and immunohistochemistry. In in vivo experiments, mice were subjected to destabilization of the medial meniscus (DMM) and given curcumin orally for 6 weeks. Cartilage integrity was evaluated by OARSI (Osteoarthritic Research Society International) scores. Results: Curcumin significantly inhibited the IL-1β-induced reduction of cell viability, degradation of ECM, and the expression of SOX9, Col2α, and AGG (P<0.01). Western blotting, immunofluorescence and immunohistochemistry experiments demonstrated that curcumin dramatically inhibited the activation of NF-κB/HIF-2α in chondrocytes treated with IL-1β (P<0.01). The articular scores were significantly lower in the DMM-induced OA mice compared to OA mice treated with curcumin (P<0.01). Conclusions: Curcumin may have the potential to inhibit OA development, partly through suppressing the activation of the NF-κB/HIF-2α pathway.

Effect of Dietary Polyphenols on Osteoarthritis—Molecular Mechanisms

“…Curcumin is the most researched type of curcuminoid due to its potent antioxidant, anti-inflammatory, antimicrobial, antirheumatic, neuroprotective, anticancer, hepatoprotective, and cardioprotective properties [ 68 ]. Several studies have reported the pain-alleviating properties and the chondroprotective effects of curcumin and curcuminoids in clinical, in vivo, and in vitro studies [ 58 , 59 , 60 , 61 , 62 , 63 , 64 ] ( Table 1 ).…”

“…Another in vitro study also confirmed the anti-inflammatory effects of curcumin, where IL-1β-induced inflammation was reduced and the mRNA expression of COL-II and SOX9 in chondrocytes were downregulated. Further immunofluorescence and immunohistochemistry studies revealed that curcumin drastically reduced the activation of NF-κB/HIF-2α in IL-1β-induced chondrocytes [ 64 ].…”

“…Ameliorated the pathophysiology ↓ joint degradation and exhibited chondroprotective effect in OA-induced rat model [ 61 , 62 , 63 , 64 ]…”

“…↓ expression of COLIIa and SOX9; ↓ overexpression of iNOS and COX-2 and suppress the activation of the NF-κB/HIF-2α pathway [ 64 ]…”

Modulation of Inflammation by Plant-Derived Nutraceuticals in Tendinitis

“…With regard to chronic musculoskeletal disorders, such as RA, osteoporosis, or OA, various polyphenols have been found to reduce inflammation and, in addition, exhibit tissue-protective and regeneration-stimulating effects [ 36 , 92 , 93 , 125 ] due to their ability to modulate dysregulated pro-inflammatory pathways back to physiological conditions, and, more so, to stimulate anabolic processes in the respective tissues, helping them to regenerate and heal [ 36 , 126 , 127 , 128 , 129 ]. Additionally, in tendinitis, as a very common and painful condition disabling musculoskeletal functionality and still lacking sustainable treatment, various plant-derived compounds have been demonstrated to affect inflammation and promote tissue healing, thus representing promising bio-active treatment agents in tendinitis therapy [ 10 , 14 , 36 , 62 , 65 , 130 , 131 , 132 , 133 ].…”