A novel pathophysiological mechanism for osteoporosis suggested by an in vivo gene expression study of circulating monocytes

Yao Zhong Liu, Volodymyr Dvornyk, Yan Lu, Hui Shen, Joan M. Lappe, Robert R. Recker, Hong Wen Deng

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Abstract

Bone mineral density (BMD) is a major risk factor for osteoporosis. Circulating monocytes may serve as early progenitors of osteoclasts and produce a wide variety of factors important to bone metabolism. However, little is known about the roles of circulating monocytes in relation to the pathophysiology of osteoporosis. Using the Affymetrix HG-U133A GeneChip® array, we performed a comparative gene expression study of circulating monocytes in subjects with high and low BMD. We identified in total 66 differentially expressed genes including some novel as well as some already known to be relevant to bone metabolism. Three genes potentially contributing to bone metabolism, CCR3 (chemokine receptor 3), HDC (histidine decarboxylase, i.e. the histamine synthesis enzyme), and GCA (glucocorticoid receptor), were confirmed by quantitative real-time reverse transcriptase-PCR as up-regulated in subjects with lower BMD. In addition, significant negative correlation was observed between expression levels of the genes and BMD Z-scores. These three genes and/or their products mediate monocyte chemotaxis, histamine production, and/or sensitivity to glucocorticoids. Our results suggest a novel pathophysiological mechanism for osteoporosis that is characterized by increased recruitment of circulating monocyte into bone, enhanced monocyte differentiation into osteoclasts, as well as osteoclast stimulation via monocyte functional changes. This is the first in vivo microarray study of osteoporosis in humans. The results may contribute to identification of new genes and their functions for osteoporosis and suggest genetic markers to discern individuals at higher risk to osteoporosis with an aim for preventive intervention and treatment.

Original languageEnglish
Pages (from-to)29011-29016
Number of pages6
JournalJournal of Biological Chemistry
Volume280
Issue number32
DOIs
StatePublished - Aug 12 2005

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Gene expression
Osteoporosis
Monocytes
Bone
Gene Expression
Bone Density
Genes
Osteoclasts
Minerals
Bone and Bones
Metabolism
Histamine
Histidine Decarboxylase
Chemokine Receptors
Glucocorticoid Receptors
Chemotaxis
Reverse Transcriptase Polymerase Chain Reaction
Genetic Markers
RNA-Directed DNA Polymerase
Glucocorticoids

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

A novel pathophysiological mechanism for osteoporosis suggested by an in vivo gene expression study of circulating monocytes. / Liu, Yao Zhong; Dvornyk, Volodymyr; Lu, Yan; Shen, Hui; Lappe, Joan M.; Recker, Robert R.; Deng, Hong Wen.

In: Journal of Biological Chemistry, Vol. 280, No. 32, 12.08.2005, p. 29011-29016.

Research output: Contribution to journalArticle

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