PMID- 18433299
OWN - NLM
STAT- MEDLINE
DCOM- 20080808
LR  - 20211020
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Print)
IS  - 0884-0431 (Linking)
VI  - 23
IP  - 5
DP  - 2008 May
TI  - In vivo genome-wide expression study on human circulating B cells suggests a 
      novel ESR1 and MAPK3 network for postmenopausal osteoporosis.
PG  - 644-54
LID - 10.1359/jbmr.080105 [doi]
AB  - 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).
FAU - Xiao, Peng
AU  - Xiao P
AD  - Osteoporosis Research Center and Department of Biomedical Sciences, Creighton 
      University, Omaha, Nebraska, USA.
FAU - Chen, Yuan
AU  - Chen Y
FAU - Jiang, Hui
AU  - Jiang H
FAU - Liu, Yao-Zhong
AU  - Liu YZ
FAU - Pan, Feng
AU  - Pan F
FAU - Yang, Tie-Lin
AU  - Yang TL
FAU - Tang, Zi-Hui
AU  - Tang ZH
FAU - Larsen, Jennifer A
AU  - Larsen JA
FAU - Lappe, Joan M
AU  - Lappe JM
FAU - Recker, Robert R
AU  - Recker RR
FAU - Deng, Hong-Wen
AU  - Deng HW
LA  - eng
GR  - R01 AG026564/AG/NIA NIH HHS/United States
GR  - R21 AG027110/AG/NIA NIH HHS/United States
GR  - R01 GM60402/GM/NIGMS NIH HHS/United States
GR  - K01 AR002170/AR/NIAMS NIH HHS/United States
GR  - R21 AG027110-01A1/AG/NIA NIH HHS/United States
GR  - R01 AR050496/AR/NIAMS NIH HHS/United States
GR  - K01 AR02170-01A2/AR/NIAMS NIH HHS/United States
GR  - P50 AR055081/AR/NIAMS NIH HHS/United States
GR  - R01 GM060402/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - B-Lymphocytes/*metabolism
MH  - Bone Density
MH  - Estrogen Receptor alpha/*genetics
MH  - Female
MH  - *Genome, Human
MH  - Humans
MH  - Mitogen-Activated Protein Kinase 3/*genetics
MH  - Osteoporosis/*genetics
MH  - *Postmenopause
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC2674539
EDAT- 2008/04/25 09:00
MHDA- 2008/08/09 09:00
PMCR- 2009/05/01
CRDT- 2008/04/25 09:00
PHST- 2008/04/25 09:00 [pubmed]
PHST- 2008/08/09 09:00 [medline]
PHST- 2008/04/25 09:00 [entrez]
PHST- 2009/05/01 00:00 [pmc-release]
AID - 644 [pii]
AID - 10.1359/jbmr.080105 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2008 May;23(5):644-54. doi: 10.1359/jbmr.080105.