Differential gene expression in cultured osteoblasts and bone marrow stromal cells from patients with Pagetís disease of bone

Naot, Dorit, Bava, Usha, Matthews, Brya, Callon, Karen E, Gamble, Gamble D, Black, Michael, Song, Sarah, Pitto, Rocco P, Cundy, Tim, Cornish, Jill and Reid, Ian R (2006) Differential gene expression in cultured osteoblasts and bone marrow stromal cells from patients with Pagetís disease of bone. Journal of Bone and Mineral Research, 22 2: 298-309. doi:10.1359/JBMR.061108


Author Naot, Dorit
Bava, Usha
Matthews, Brya
Callon, Karen E
Gamble, Gamble D
Black, Michael
Song, Sarah
Pitto, Rocco P
Cundy, Tim
Cornish, Jill
Reid, Ian R
Title Differential gene expression in cultured osteoblasts and bone marrow stromal cells from patients with Pagetís disease of bone
Journal name Journal of Bone and Mineral Research   Check publisher's open access policy
ISSN 0884-0431
Publication date 2006-11-13
Year available 2006
Sub-type Article (original research)
DOI 10.1359/JBMR.061108
Volume 22
Issue 2
Start page 298
End page 309
Total pages 12
Editor Thomas L Clemens
Place of publication America
Publisher American Society for Bone and Mineral Research
Language eng
Subject 06 Biological Sciences
1004 Medical Biotechnology
11 Medical and Health Sciences
0104 Statistics
92 Health
Abstract Paget's disease is a focal condition of bone. To study changes in cells within pagetic lesions, we cultured osteoblasts and stromal cells from 22 patients and compared gene expression in these cells to cells from healthy bone. We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions. Introduction: Paget's disease is a focal condition of bone of unknown cause. Although it is regarded as primarily an osteoclast disorder, the tight coupling of the activity of osteoclasts and osteoblasts suggests that the osteoblast could play a key role in its pathogenesis. The aim of the study was to identify possible changes in pagetic osteoblasts and stromal cells that might contribute to the development of pagetic lesions. Materials and Methods: Candidate genes were identified based on known bone cell regulators, supplemented with microarray analysis. Gene expression was determined by real-time PCR in primary cultures of osteoblasts and bone marrow stromal cells from pagetic patients and control subjects. Concentrations of secreted proteins were determined by ELISA. Results: Dickkopf1 mRNA and protein levels were increased in both pagetic osteoblast and stromal cell cultures, and interleukin (IL)-1 and IL-6 were overexpressed in pagetic osteoblasts. These changes parallel recent findings in myeloma bone disease, which shares some clinical similarities with Paget's disease. Alkaline phosphatase was overexpressed, and bone sialoprotein and osteocalcin were underexpressed in pagetic osteoblasts, consistent with their circulating levels in pagetic patients. It is hypothesized that overexpression of Dickkopf1, IL-1, and IL-6 would result in stimulation of osteoclast proliferation and inhibition of osteoblast growth, leading to the development of the characteristic lytic bone lesions. By stimulating osteoblast differentiation, Dickkopf1 and IL-6 may also promote mineralization, leading to the conversion of lytic lesions to sclerotic. Conclusions: These findings suggest that dysregulated gene expression in pagetic osteoblasts could cause the changes in bone cell number and function characteristic of Paget's disease.
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Nursing and Midwifery Publications
 
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