Effect of menopause on gene expression pattern in bone tissue of nonosteoporotic women.

Objective: Menopausal changes influence the growth, differentiation, and metabolism of bone tissue. Hormonal deficiency at the time of menopause results in marked increases in bone resorption and formation, leading to rapid bone loss. The aim of our investigation was to determine genes characterized by significantly changed mRNA expression rates in postmenopausal versus premenopausal nonosteoporotic bone tissue and to describe the interrelationships among these genes using multivariate data analysis. Methods: Ten bone tissue samples from postmenopausal nonosteoporotic women and seven bone tissue samples from premenopausal nonosteoporotic women were examined. The expression differences of 118 selected genes were analyzed in a TaqMan probe-based quantitative reverse transcriptase-poly in erase chain reaction system. Results: The Mann-Whitney U test indicated significant differences in the expression of 29 genes of postmenopausal and premenopausal nonosteoporotic women. Twenty-eight genes, including extracellular matrix molecules and digesting enzymes, genes belonging to the transforming growth factor-beta/bone morphogenic protein pathway, transcription factors, growth factors, and other candidate genes, were significantly up-regulated in postmenopausal women compared with premenopausal women. Only one gene (ENO1) showed down-regulation after menopause. Based on the multiple mRNA expression profiles of 118 genes, postmenopausal and premenopausal states could be differentiated by enhanced postmenopausal gene expression levels using principal components analysis. Canonical variates analysis demonstrated that postmenopausal and premenopausal nonosteoporotic bone tissues can be distinguished by expression analysis of genes controlled via estrogen receptor-alpha and genes coding for extracellular matrix molecules. Conclusions: The menopausal state of bone tissue has been unambiguously defined by its complex gene transcription pattern. Significant differences observed in the gene expression profiles of estrogen-deficient human bone tissue provide further insight into the process of postmenopausal changes of bone metabolism.