Influence of corticosteroids on interleukin-1β-stimulated equine chondrocyte gene expression.

The research investigated how two types of corticosteroids—triamcinolone acetonide (TA) and methylprednisolone acetate (MPA)—affect the expression of certain genes in horse cartilage cells when stimulated by the protein interleukin-1β. The study found no significant differences between the effect of the two corticosteroids.

Research Methodology

• The study involved in vitro experiments using articular cartilage samples from 2- to 3-year-old horses.
• The cartilage was exposed to a synthetic version of interleukin-1β (reIL-1β) in the presence and absence of the corticosteroids TA and MPA.
• Exposure levels for the corticosteroids were set at 10(-7) and 10(-6) Molar (a measure of concentration).
• The researchers studied the resting mRNA levels of anabolic and catabolic genes produced by chondrocyte cells (cartilage cells).
• Messenger RNA (mRNA) was measured using quantitative PCR (qPCR) after 6 and 12-hour incubations.

Gene Targets

• The genes of interest for the study included aggrecan and collagen II genes (important structural proteins in cartilage), various enzymes and inhibitors involved in tissue degradation and repair (MMP3, MMP 13, aggrecanase 1, and TIMP 1 & 2), and genes related to apoptosis (cell death) and inflammation (BCL 2, vascular endothelial growth factor, and COX 2).

Key Findings

• Interleukin-1β significantly influenced the expression of most transcripts—i.e., it affected gene activity.
• Both MPA and TA blocked the induction of the enzyme MMP 13, a matrix metalloproteinase known to degrade collagen, after 6 and 12 hours. This effect was significant at 6 hours with MPA at 10(-7) M and TA at 10(-6) M.
• COX 2, a substance that mediates inflammation in the body, was induced by reIL-1β, and both MPA and TA significantly halted its upregulation—i.e., prevented it from increasing.
• TIMP 2 expression, which is involved in inhibiting matrix metalloproteinases, was reduced by reIL-1β, but was significantly alleviated by both MPA and TA.
• Importantly, there were no significant differences observed between the effects of the two corticosteroids on any of the genes studied.

Study Conclusion

• Based on these results, the study suggests that any differing effects between the corticosteroids MPA and TA on cartilage cell metabolism must happen after the protein translation phase. In other words, any differences likely occur later in the protein production process, not at the gene expression level.