Functional changes in osteogenic, adipogenic, and hematopoietic cell populations appear to be involved in the pathogenesis of osteoporosis, Australian scientists have shown.
The study, by Blair Hopwood’s team at the University of Adelaide, used gene microarray analysis to compare the expression levels of many thousands of candidate osteoporosis disease genes.
They extracted genetic material from trabecular bone from the intertrochanteric region from three sets of age-matched women: 11 with an osteoporotic fracture, 14 with primary osteoarthritis, and 11 with no known bone pathology.
Real-time polymerase chain reaction analysis identified 32 genes that were differentially expressed in osteoporotic bone. Hopwood’s team was able to classify these candidate genes into three groups based on function: osteoblast maturation; myelomonocytic differentiation and osteoclastogenesis; and adipogenesis, lipid and/or glucose metabolism.
Many of these genes have known or suspected roles in bone metabolism, say the authors, and some have previously been implicated in the pathogenesis of osteoporosis.
The results are therefore consistent with previously suggested underlying molecular mechanisms for osteoporosis that include altered osteoblast and osteoclast differentiation and function, and an imbalance between osteoblastogenesis and adipogenesis.
Although unable to determine causality, Hopwood et al conclude that their results “provide new genome-wide insights into the altered gene expression present in the microenvironment of osteoporotic bone and may prove useful in developing a better understanding of the cellular and molecular mechanisms that lead to fragility fractures.”