In Vivo Genome-Wide Expression Study on Human Circulating B Cells Suggests a NovelESR1andMAPK3Network for Postmenopausal Osteoporosis
Year: 2008
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Osteoporosis is characterized by low BMD. Studies have shown that B cells may participate in osteoclastogenesis through expression of osteoclast-related factors, such as RANKL, transforming growth factor beta (TGFB), and osteoprotegerin (OPG). However, the in vivo significance of B cells in human bone metabolism and osteoporosis is still largely unknown, particularly at the systematic gene expression level. MATERIALS AND METHODS: In this study, Affymetrix HG-U133A GeneChip arrays were used to identify genes differentially expressed in B cells between 10 low and 10 high BMD postmenopausal women. Significance of differential expression was tested by t-test and adjusted for multiple testing with the Benjamini and Hochberg (BH) procedure (adjusted p </= 0.05). RESULTS: Twenty-nine genes were downregulated in the low versus high BMD group. These genes were further analyzed using Ingenuity Pathways Analysis (Ingenuity Systems). A network involving estrogen receptor 1 (ESR1) and mitogen activated protein kinase 3 (MAPK3) was identified. Real-time RT-PCR confirmed differential expression of eight genes, including ESR1, MAPK3, methyl CpG binding protein 2 (MECP2), proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), Scr-like-adaptor (SLA), serine/threonine kinase 11 (STK11), WNK lysine-deficient protein kinase 1 (WNK1), and zinc finger protein 446 (ZNF446). CONCLUSIONS: This is the first in vivo genome-wide expression study on human B cells in relation to osteoporosis. Our results highlight the significance of B cells in the etiology of osteoporosis and suggest a novel mechanism for postmenopausal osteoporosis (i.e., that downregulation of ESR1 and MAPK3 in B cells regulates secretion of factors, leading to increased osteoclastogenesis or decreased osteoblastogenesis).
DOI: 10.1359/jbmr.080105
Authors: Peng Xiao, Yuan Chen, Hui Jiang, Yao-Zhong Liu, Feng Pan, Tie-Lin Yang, Zi-Hui Tang, Jennifer A Larsen, Joan M Lappe, Robert R Recker, Hong-Wen Deng
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: 人类复杂性状的分子与统计遗传学研究, G2510581341, Genomic Convergence for Female Osteoporosis Risk Genes, Genomic search for bone mass QTLs, G3997843383, Robust and Powerful Test of Candidate Genes to Bone Mass, CHARACTERIZATION OF DELETERIOUS GENOMIC MUTATIONS, 对中国首例“家族性成年人肌阵挛癫痫（FAME）”大家系的致病基因定位研究和亚型鉴定, Genetic Basis of Osteoporotic Fractures and Bone Mass, Proteomics Study of Peripheral Blood Monocytes on Osteoporosis
OpenAlex ID: W2064016072