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In Vivo Genome‐Wide Expression Study on Human Circulating B Cells Suggests a Novel ESR1 and MAPK3 Network for Postmenopausal Osteoporosis
Author(s) -
Xiao Peng,
Chen Yuan,
Jiang Hui,
Liu YaoZhong,
Pan Feng,
Yang TieLin,
Tang ZiHui,
Larsen Jennifer A,
Lappe Joan M,
Recker Robert R,
Deng HongWen
Publication year - 2008
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.080105
Subject(s) - osteoprotegerin , biology , rankl , estrogen receptor alpha , osteoclast , osteoporosis , cancer research , endocrinology , estrogen receptor , microbiology and biotechnology , receptor , genetics , activator (genetics) , breast cancer , cancer
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 β (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).