Faculty Collaboration Database

A novel pathophysiological mechanism for osteoporosis suggested by an in vivo gene expression study of circulating monocytes. J Biol Chem 2005 Aug 12;280(32):29011-6

Date

06/21/2005

Pubmed ID

15965235

DOI

10.1074/jbc.M501164200

Scopus ID

2-s2.0-23844495088 (requires institutional sign-in at Scopus site)   117 Citations

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(R) 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 GCR (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.

Author List

Liu YZ, Dvornyk V, Lu Y, Shen H, Lappe JM, Recker RR, Deng HW

MESH terms used to index this publication - Major topics in bold

Aged
Algorithms
Bone Density
Chemotaxis
Female
Gene Expression Regulation
Glucocorticoids
Histidine Decarboxylase
Humans
Lumbar Vertebrae
Middle Aged
Models, Biological
Monocytes
Oligonucleotide Array Sequence Analysis
Osteoporosis
Receptors, CCR3
Receptors, Chemokine
Receptors, Glucocorticoid
Reverse Transcriptase Polymerase Chain Reaction
Risk Factors