In vivo genome-wide expression study on human circulating B cells suggests a novel ESR1 and MAPK3 network for postmenopausal osteoporosis

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

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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).

Original languageEnglish
Pages (from-to)644-654
Number of pages11
JournalJournal of Bone and Mineral Research
Volume23
Issue number5
DOIs
StatePublished - May 2008

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Postmenopausal Osteoporosis
Mitogen-Activated Protein Kinase 3
Estrogen Receptor alpha
B-Lymphocytes
Genome
Osteoporosis
Osteogenesis
Down-Regulation
Methyl-CpG-Binding Protein 2
Genes
Protein Phosphatase 1
Gene Expression
Osteoprotegerin
Phosphoprotein Phosphatases
Protein-Serine-Threonine Kinases
Zinc Fingers
Transforming Growth Factors
Osteoclasts
Proline
Protein Kinases

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

In vivo genome-wide expression study on human circulating B cells suggests a novel ESR1 and MAPK3 network for postmenopausal osteoporosis. / Xiao, Peng; Chen, Yuan; Jiang, Hui; Liu, Yao Zhong; Pan, Feng; Yang, Tie Lin; Tang, Zi Hui; Larsen, Jennifer A.; Lappe, Joan M.; Recker, Robert R.; Deng, Hong Wen.

In: Journal of Bone and Mineral Research, Vol. 23, No. 5, 05.2008, p. 644-654.

Research output: Contribution to journalArticle

Xiao, Peng ; Chen, Yuan ; Jiang, Hui ; Liu, Yao Zhong ; Pan, Feng ; Yang, Tie Lin ; Tang, Zi Hui ; Larsen, Jennifer A. ; Lappe, Joan M. ; Recker, Robert R. ; Deng, Hong Wen. / In vivo genome-wide expression study on human circulating B cells suggests a novel ESR1 and MAPK3 network for postmenopausal osteoporosis. In: Journal of Bone and Mineral Research. 2008 ; Vol. 23, No. 5. pp. 644-654.
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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).",
author = "Peng Xiao and Yuan Chen and Hui Jiang and Liu, {Yao Zhong} and Feng Pan and Yang, {Tie Lin} and Tang, {Zi Hui} and Larsen, {Jennifer A.} and Lappe, {Joan M.} and Recker, {Robert R.} and Deng, {Hong Wen}",
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T1 - In vivo genome-wide expression study on human circulating B cells suggests a novel ESR1 and MAPK3 network for postmenopausal osteoporosis

AU - Xiao, Peng

AU - Chen, Yuan

AU - Jiang, Hui

AU - Liu, Yao Zhong

AU - Pan, Feng

AU - Yang, Tie Lin

AU - Tang, Zi Hui

AU - Larsen, Jennifer A.

AU - Lappe, Joan M.

AU - Recker, Robert R.

AU - Deng, Hong Wen

PY - 2008/5

Y1 - 2008/5

N2 - 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).

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 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).

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