Gene Expression Profiling in Paget's Disease of Bone: Upregulation of Interferon Signaling Pathways in Pagetic Monocytes and Lymphocytes

• Published in: Journal of bone and mineral research Vol. 23; no. 2; pp. 253 - 259
• Main Authors: Nagy, Zsolt B, Gergely, Péter, Donáth, Judit, Borgulya, Gábor, Csanád, Mónika, Poór, Gyula
• Format: Journal Article
• Language: English
• Published: Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01.02.2008; American Society for Bone and Mineral Research
• Subjects: Adult; Aged; Aged, 80 and over; Base Sequence; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; gene expression; Gene Expression Profiling; Humans; interferon; Interferon-gamma - blood; Interferon-gamma - genetics; Interferon-gamma - metabolism; lymphocyte; Lymphocytes - pathology; Male; Middle Aged; Molecular Sequence Data; monocyte; Monocytes - pathology; Osteitis Deformans - genetics; Paget's disease of bone; Signal Transduction - genetics; Signal Transduction - immunology; Skeleton and joints; Vertebrates: osteoarticular system, musculoskeletal system; Osteoarticular system; Signal transduction; Vertebrata; Mammalia; Monocyte; Cytokine; Interferon; Gene expression; Lymphocyte; Paget's disease of bone
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.071021

We examined the gene expression profile of genes involved in bone metabolism in 23 patients with PD compared with 23 healthy controls. We found a significant overexpression of the genes of the IFN pathway along with a downregulation of tnf‐α. Our result suggest that IFN‐mediated signaling may play important roles in aberrant osteoclastogenesis of PD. Introduction: Paget's disease of bone (PD) is characterized by focal regions of highly exaggerated bone remodeling and aberrant osteoclastogenesis. Under physiological conditions, circulating monocytes may serve as early progenitors of osteoclasts and along with peripheral blood lymphocytes produce a wide variety of factors important in bone metabolism. Nevertheless, little is known about the roles of circulating monocytes and lymphocytes in relation to the pathological bone turnover in PD. Materials and Methods: In this study, we aimed at investigating the gene expression pattern of PD using quantitative real‐time PCR in monocytes and lymphocytes isolated from peripheral blood mononuclear cells (PBMCs). Fifteen genes known to be involved in osteoclastogenesis were studied in cells from 23 patients with PD and in cells from 23 healthy controls. Eight human genes including ifn‐α (3.48‐fold, p < 0.001), ifn‐β (2.68‐fold, p < 0.001), ifn‐γ (1.98‐fold, p = 0.002), p38 β2 mapk (2.47‐fold, p = 0.002), ifn‐γr1 (2.03‐fold, p = 0.01), ifn‐γr2 (1.81‐fold, p = 0.02), stat1 (1.57‐fold, p = 0.037), and tnf‐α (−2.34, p < 0.001) were found to be significantly altered in pagetic monocytes compared with monocytes of healthy controls. Results: In pagetic lymphocytes, significant changes in the expression of ifn‐α (2.17‐fold, p < 0.001), ifn‐β (2.13‐fold, p = 0.005), ifn‐γ (1.89‐fold, p < 0.001), ifn‐γr1 (1.02‐fold, p = 0.04), ifn‐γr2 (1.01‐fold, p = 0.031), stat2 (1.79‐fold, p < 0.001), and tnf‐α (−1.49, p < 0.001) were found compared with lymphocytes of healthy controls. Furthermore, IFN‐γ protein was significantly elevated in the sera of PD patients (18.7 ± 6.69 pg/ml) compared with healthy controls (3.87 ± 6.48 pg/ml, p = 0.042). Conclusions: In conclusion, our data suggest that novel pathways mainly related to the IFN‐mediated signaling may play important roles in the aberrant osteoclastogenesis of PD.