Background: Osteoarthritis (OA) represents one of the most common musculoskeletal diseases and is a major cause of reduced quality of life. Despite its high clinical burden, no curative treatment is currently available. While severe OA is predominantly managed with joint replacement, there is considerable interest in less invasive treatment modalities. Intra-articular glucocorticoid injections, such as triamcinolone and methylprednisolone, are commonly administered due to their proven short-term pain relief and are often used as adjunctive or bridging therapies. However, previous studies suggest that triamcinolone may exert chondrotoxic effects. Evidence on the broader impact of glucocorticoids on cartilage biology and structural integrity, however, remains limited.
Objective: The objective of this study was to gain a deeper understanding of how the commonly used synthetic glucocorticoid triamcinolone acetonide (TA) affects viability, gene expression and metabolism of human cartilage cells (chondrocytes).
Methods: Human chondrocytes were harvested from femoral head cartilage obtained during joint replacement surgeries. Following expansion, cells were encapsulated in alginate beads and cultured within this three-dimensional matrix to more closely recapitulate physiological conditions. After three weeks, cells were cultured in inflammatory medium (supplemented with 1 ng/mL IL-1b and 1 ng/mL TNFA) for two weeks to simulate the inflammatory environment characteristic of osteoarthritic joints. In the second week, cells were subsequently treated with TA and then collected for analysis. Experimental and control groups differed based on inflammatory versus non-inflammatory conditions, low versus high TA dosage, and single versus continuous TA exposure. Outcome measures included cell viability, quantitative PCR-based gene expression analysis and evaluation of cartilage-like matrix production. Samples from ten donors were analysed.
Results: Cell viability assays demonstrated comparable viability across all experimental groups. Preliminary PCR findings based on one donor showed that the exposure to inflammatory mediators increased the gene expression of inflammatory markers, including interleukins (IL-1b, IL-6, IL-8), tumour necrosis factor alpha (TNFA), and cyclooxygenase-2 (COX2). Treatment with TA reduced the expression of these markers across all TA concentrations and under both inflammatory and non-inflammatory conditions. Markers associated with a healthy cartilage phenotype, including collagen type II (COL2A1), aggrecan (ACAN), and transcription factor SOX9, were downregulated in TA-treated groups. Similarly, hypertrophic markers (COL10A1 and RUNX2) were suppressed following TA treatment. Catabolic genes involved in cartilage degradation, including matrix metalloproteinases (MMP3 and MMP13) and aggrecanases (ADAMTS4 and ADAMTS5), were upregulated under inflammatory conditions in the absence of TA, whereas TA treatment reduced their expression both in the presence and absence of inflammation.
Conclusion: Simulated inflammatory conditions successfully induced a pronounced inflammatory response at the gene expression level. Treatment with triamcinolone acetonide (TA) attenuated this response, suppressed chondrocyte hypertrophic differentiation, and reduced the expression of enzymes involved in cartilage degradation and remodeling. These findings indicate a protective effect of intra-articular application of TA against inflammation-driven tissue damage in osteoarthritic joints. However, the concurrent downregulation of genes associated with cartilage homeostasis points to a potential trade-off, suggesting impaired cartilage regeneration and metabolism.