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 (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 (), 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 and NF-κB subunits were analyzed by qRT-PCR. Celecoxib and GS alone or co-incubated with significantly reduced expression and release of cyclooxygenase (, prostaglandin (, , , tumor necrosis factor (, and , while it increased , compared to baseline or . Both drugs reduced apoptosis and superoxide production; reduced the expression of superoxide dismutase, catalase, and nuclear factor erythroid; increased ; and limited and . Celecoxib and GS combination demonstrated an increased inhibitory effect on 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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396455 | PMC |
http://dx.doi.org/10.3390/ijms22168980 | DOI Listing |
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