Abstract
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-polymerase 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-β/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-α 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.
