Gene expression profiling of bone marrow stromal cells from juvenile, adult, aged and osteoporotic rats: with an emphasis on osteoporosis.

Purpose: Osteoporosis is a multi-factorial, age-related disease with a complex etiology and mode of regulation involving a large numbers of genes. To better understand the possible relationships among genes, we fingerprinted genes in a rat model induced by ovariectomy to determine differences among osteoporotic, non-osteoporotic, aged and juvenile rats.

Methods: We applied genome wide cDNA microarray technology to analyze genes expressed in bone marrow mesenchymal stromal cells (BMSC) and compared non-osteoporotic adult vs. osteoporotic, non-osteoporotic adult vs. aged, and non-osteoporotic adult vs. juvenile. Rigorous statistical analysis of functional annotation (EASE program) identified over-represented biological and molecular functions with significant group wide changes (p< or =0.05). Some of the expressed genes were further confirmed by quantitative RT-PCR (reverse transcription-polymerase chain reaction).

Results: Differences in gene expression were observed by identifying transcripts selected by t-test that were consistently changed by a minimum of two-fold. There were 195 transcripts that showed an increased expression and 109 transcripts that showed decreased expression relative to the osteoporotic condition. Of these, 75% transcripts were unknown gene products or ESTs (expressed sequence tag). A number of genes found in the aged and juvenile groups were not present in the osteoporotic rats. Functional clustering of the genes using the EASE bioinformatics program revealed that transcripts in osteoporosis were associated with signal transduction, lipid metabolism, protein metabolism, ionic and protein transport, neuropeptide and G protein signaling pathways. Although some of the genes have previously been shown to play a key role in osteoporosis, several genes were uniquely identified in this study and likely play a role in developing aged related osteoporosis that could have compelling implications in the development of new diagnostic strategies and therapeutics for osteoporosis.

Conclusions: These data suggest that osteoporosis is associated with changes of multiple novel gene expression and that numerous pathways could play important roles in osteoporosis pathogenesis.