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The following is a summary of “Dexamethasone: a double-edged sword in the treatment of osteoarthritis,” published in the April 2025 issue of Scientific Reports by Tarasova et al. 

Glucocorticoids help relieve osteoarthritis symptoms but raise safety concerns. Their long-term effects on chondrocytes remain unclear. 

Researchers conducted a retrospective study to assess the effects of dexamethasone (DEX) and triamcinolone acetonide (TA) on chondrocytes. 

They evaluated the effects of DEX and TA on the expression of pro-inflammatory genes in inflamed chondrocytes. They analyzed DEX-treated chondrocytes using next-generation sequencing, high-resolution mass spectrometry, proliferation and metabolic rate assays, wound healing capacity, and senescence-associated β-galactosidase staining. 

The results showed a single therapeutic dose of DEX (40 nM) reduced inflammatory gene expression in chondrocytes, while TA showed no effect. DEX reduced inflammation and ECM production. At 24 h, DEX led to 168 differentially expressed genes (DEGs) vs. untreated inflamed cells, dropping to 5 DEGs by 48 h. The difference between DEX-treated and healthy cells increased from 666 DEGs at 24 h to 1,317 DEGs at 48 h. Pathway analysis showed disruptions in cell cycle, mitosis, and ECM homeostasis. Repeated DEX doses (40 nM and 1 µM) induced senescence in healthy cells but not in inflamed ones. High-dose DEX reduced Caspase 3/7 in inflamed but not healthy cells. 

Investigators found that DEX transiently suppressed inflammation but reduced ECM production and induced senescence in healthy chondrocytes at therapeutic doses. High-dose DEX reduced apoptosis in inflamed cells, indicating the need for caution with intra-articular use. 

Source: nature.com/articles/s41598-025-96050-2