Differential gene expression and protein expression levels of MMP and TIMP molecules in response to glucocorticoid treatment in arthritic patients

Objectives

In this study we attempted to map the molecular events that underlie the clinical effects of glucocorticoid (GC) treatment in patients.

Methods

DNA arrays and immunohistochemical staining was used for comparison of patient material isolated before and after intra-articular glucocorticoid (GC) treatment. Gene expression data analysis was performed in the GeneSpring™ software.

Results

Hierarchical clustering of gene expression data could distinguish samples taken before from those taken after treatment to a surprisingly high degree, in spite of anticipated individual and experimental variations. Patterns were further analyzed by identification of genes with both statistically significant differential expression (P < 0.05) using the cross gene error model implemented in GeneSpring™, and greater than twofold differential expression. Twelve genes satisfying both of these criteria were found, including matrix metalloproteinase (MMP)-1 and MMP-3, for which mRNA expression was downregulated, and tissue inhibitor of MMP (TIMP)-1 and TIMP-4, for which mRNA expression was upregulated by GC treatment. Immunohistochemical staining for several MMP and TIMP molecules confirmed data for MMP-1 and MMP-3 on a protein level, whereas the result for TIMP-1 and other TIMPs revealed reduced protein expression of these molecules.

Conclusions

Our data demonstrate that DNA arrays may be used for evaluating the molecular effects of novel as well as established therapies, but also that data should be interpreted with caution concerning their ability to predict therapeutic effects at the protein level.