Gene expression patterns in the bone tissue of women with fibrous dysplasia

Abstract

Fibrous dysplasia is an isolated skeletal disorder caused by a somatic activating mutation of GNAS gene with abnormal unmineralized matrix overproduction and extensive undifferentiated bone cell accumulation in the fibro-osseous lesions. The aim of our investigation was to identify genes that are differently expressed in fibrous versus non-fibrous human bone and to describe the relationships between these genes using multivariate data analysis. Six bone tissue samples from female patients with fibrous dysplastia (FD) and seven bone tissue samples from women without FD (non-FD) were examined. The expression differences of selected 118 genes were analyzed by the TaqMan probe-based quantitative real-time RT-PCR system. The Mann-Whitney U-test indicated marked differences in the expression of 22 genes between FD and non-FD individuals. Nine genes were upregulated in FD women compared to non-FD ones and 18 genes showed a downregulated pattern. These altered genes code for minor collagen molecules, extracellular matrix digesting enzymes, transcription factors, adhesion molecules, growth factors, pro-inflammatory cytokines, and lipid metabolism-affected substrates. Canonical variates analysis demonstrated that FD and non-FD bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via a G-protein coupled pathway and BMP cascade as well as genes coding for extracellular matrix composing molecules. The remarkable changed gene expression profile observed in the fibrous dysplastic human bone tissue may provide further insight into the pathogenetic process of fibrous degeneration of bone.

Autosomal dominant mesomandibular fibro-osseous dysplasia: a self-resolving inherited fibro-osseous lesion of the jaws

“…With time, mutated cells population is decreased with normal cells predominating thus leading to arrested growth of lesions. A recent study comparing bone tissue samples from patients with fibrous dysplasia to patients without it, besides confirming the involvement of G protein coupled pathway, implicated also BMP signaling pathway in the pathogenesis of these lesions (Kiss et al, 2010). Fibrous dysplasia and non-fibrous dysplasia subjects could be clearly separated by differences in the expression of BMP2, BMP4, BMPR1A, BMPR2, and other members of the BMP pathway.…”

“…In our opinion, the term autosomal dominant mesomandibular fibro-osseous dysplasia (ADMFOD) best describes this condition. In addition, since misregulation of the Bone Morphogenetic Protein (BMP) pathway has been suggested to play a role in the pathogenesis of fibrous lesions in the bone (Kiss et al, 2010), we examined (by immunohistochemistry) if BMP binding protein Twisted Gastrulation (TWSG1) is present in either bone cells or fibrous tissue within the lesion in one of the affected members.…”

Gene Expression Changes in Femoral Head Necrosis of Human Bone Tissue

“…postmenopausal osteoporosis, estrogenic hormone deficient human bone tissue and fibrous dysplasia). These genetic data from our laboratory have demonstrated significantly different expression patterns in various pathological conditions of bone tissue compared to the control physiological state [6][7][8][9][10].…”

“…For comparing gene expression patterns in the bone tissue of ONFH and non-ONFH subjects, we selected 117 genes based on recent literature (Supplementary table), OMIM (Online Mendelian Inheritance in Man) database, as well as our data regarding genetic pathway analysis [6,[9][10][11]. Twenty seven genes from the common TGF-beta/BMP pathway and Wingless (Wnt) cascade were selected for these studies; further 23 genes from extracellular matrix (ECM) components, 8 are involved in ECM degradation, 9 genes code growth factors, 5 genes code cell adhesion molecules, 7 genes code transcriptional factors and 12 of them are known to be controlled by estrogen and the 26 remaining genes were assorted by our previous published analyses [6,[9][10][11].…”

“…The aim of the present study was to investigate the gene expression profile of those genes in human ONFH that have previously shown alterations in other metabolic bone diseases [6][7][8][9][10]. We assumed that performing a comprehensive gene-expression study we could identify important genes with significant role in the development of this condition.…”