Abstract
This study investigated the possible anti-inflammatory and chondroprotective effects of a combination of celecoxib and prescription-grade glucosamine sulfate (GS) in human osteoarthritic (OA) chondrocytes and their possible mechanism of action. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination with IL-1β (10 ng/mL) and a specific nuclear factor (NF)-κB inhibitor (BAY-11-7082, 1 µM). Gene expression and release of some pro-inflammatory mediators, metalloproteinases (MMPs), and type II collagen (Col2a1) were evaluated by qRT-PCR and ELISA; apoptosis and mitochondrial superoxide anion production were assessed by cytometry; B-cell lymphoma (BCL)2, antioxidant enzymes, and p50 and p65 NF-κB subunits were analyzed by qRT-PCR. Celecoxib and GS alone or co-incubated with IL-1β significantly reduced expression and release of cyclooxygenase (COX)-2, prostaglandin (PG)E2, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and MMPs, while it increased Col2a1, compared to baseline or IL-1β. Both drugs reduced apoptosis and superoxide production; reduced the expression of superoxide dismutase, catalase, and nuclear factor erythroid; increased BCL2; and limited p50 and p65. Celecoxib and GS combination demonstrated an increased inhibitory effect on IL-1β than that observed by each single treatment. Drugs effects were potentiated by pre-incubation with BAY-11-7082. Our results demonstrated the synergistic effect of celecoxib and GS on OA chondrocyte metabolism, apoptosis, and oxidative stress through the modulation of the NF-κB pathway, supporting their combined use for the treatment of OA.
Highlights
IntroductionThe risk of developing OA is increased by physical inactivity and by a low-fiber diet rich in sugar and saturated fats
Our first result confirmed the significant increase in gene expression and supernatant release of the main pro-inflammatory cytokines, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and PGE2, the latter probably related to the increase in COX-2, in OA chondrocytes stimulated with IL-1β, as previously reported [22,35]
Our results demonstrate the chondroprotective role of celecoxib in OA
Summary
The risk of developing OA is increased by physical inactivity and by a low-fiber diet rich in sugar and saturated fats All these different factors are associated with an alteration of composition and function of the gut microbiota, causative of low-grade inflammation, which is an important contributor to joint damage in OA [3,4]. This microbial dysbiosis could represent the missing link between the different conditions contributing to OA pathogenesis, suggesting microbiota as a new pharmacological strategy for OA management [5,6]
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