Abstract
β-caryophyllene (BCP), a plant-derived sesquiterpene, has been reported to have anti-inflammatory and antioxidant effects. The purpose of this study is to evaluate the effects of BCP in combination with ascorbic acid (AA) and d-glucosamine (GlcN) against macrophage-mediated inflammation on in vitro primary human chondrocytes. Changes in cell viability, intracellular ROS generation, gene expression of pro-inflammatory mediators, metalloproteinases (MMPs), collagen type II and aggrecan were analyzed in primary human chondrocytes exposed to the conditioned medium (CM) of activated U937 monocytes and subsequently treated with BCP alone or in combination with AA and GlcN. The CM-induced chondrocyte cytotoxicity was reduced by the presence of low doses of BCP alone or in combination with AA and GlcN. The exposure of cells to CM significantly increased IL-1β, NF-κB1 and MMP-13 expression, but when BCP was added to the inflamed cells, alone or in combination with AA and GlcN, gene transcription for all these molecules was restored to near baseline values. Moreover, chondrocytes increased the expression of collagen type II and aggrecan when stimulated with AA and GlcN alone or in combination with BCP. This study showed the synergistic anti-inflammatory and antioxidative effects of BCP, AA and GlcN at low doses on human chondrocyte cultures treated with the CM of activated U937 cells. Moreover, the combination of the three molecules was able to promote the expression of collagen type II and aggrecan. All together, these data could suggest that BCP, AA and GlcN exert a chondro-protective action.
Highlights
Osteoarthritis (OA) is a progressive inflammatory degenerative whole-joint disease with an increasing prevalence due to aging of the population [1,2]
To gain new insights into the activity of BCP, its antioxidant, anti-inflammatory and chondro-protective effects, the present study aims to explore its effects on viability and proinflammatory molecule expression in the presence or absence of ascorbic acid (AA) and GlcN on human chondrocytes in an in vitro inflammatory model of phorbol 12-myristate 13-acetate (PMA)–lipopolysaccharides (LPS)-stimulated U937 human monocytes
The Evaluation of the Effects of BCP, Alone or in Combination with AA and GlcN on conditioned medium (CM)-Induced Chondrocyte Toxicity In Figure 1, typical results of primary human chondrocytes cultivated in the presence of different concentrations of BCP, AA and GlcN, alone or in combination, were reported
Summary
Osteoarthritis (OA) is a progressive inflammatory degenerative whole-joint disease with an increasing prevalence due to aging of the population [1,2]. Macrophage-mediated inflammation is considered one of the main drivers of both OA development and progression, and causes the release of proinflammatory cytokines, such as interleukin-1β 1. (IL-1β), and reactive oxygen species (ROS) [3,4] These molecules induce chondrocytes to synthesize other inflammatory mediators that upregulate cytokines and increase matrix metalloproteinase (MMP) activity leading to cartilage disruption, mainly due to the imbalance between synthesis and degradation of extracellular matrix (ECM) molecules, in favor of degradation [1,2,3,4]. Pharmaceuticals 2021, 14, 286 chondrocytes display epigenomic alterations leading to an alteration of nuclear factor κB (NF-κB) activation [5]. It has been shown to play a key role in the acquisition of inflammatory phenotype and cytokine-induced secretion of MMPs by chondrocytes [6,7]
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