Curcumenol mitigates chondrocyte inflammation by inhibiting the NF‑κB and MAPK pathways, and ameliorates DMM‑induced OA in mice.

Abstract

At present, an increasing number of individuals are affected by osteoarthritis (OA), resulting in a heavy socioeconomic burden. OA in knee joints is caused by the release of inflammatory cytokines and subsequent biomechanical and structural deterioration. To determine its anti-inflammatory function, the current study investigated the use of the plant-derived medicine, curcumenol, in OA treatment. Curcumenol was not cytotoxic to ATDC5 chondrocytes and primary chondrocytes, as determined using a cell viability test. When these cells were treated with TNF-α and IL-1β to induce inflammation, curcumenol treatment inhibited the progression of inflammation by inactivating the NF-κB and MAPK signaling pathways, as well as decreasing the expression levels of MMP3 (as indicated by reverse transcription-quantitative PCR and western blotting). Moreover, to analyze metabolic and catabolic status in high-density and pellet culture, catalytic changes and the degradation of the extracellular matrix induced by TNF-α and IL-1β, were evaluated by alcian blue staining. These catalytic deteriorations were ameliorated by curcumenol. Using curcumenol in disease management, the mechanical and metabolic disruption of cartilage caused in the destabilization of medial meniscus (DMM) model was prevented in vivo. Thus, curcumenol mitigated inflammation in ATDC5 chondrocytes and primary mice chondrocytes, and also ameliorated OA in a DMM-induced mouse model.