GRIP1 enhances estrogen receptor α-dependent extracellular matrix gene expression in chondrogenic cells

M. Kato, H. Takaishi, Masaki Yoda, T. Tohmonda, J. Takito, Nobuyuki Fujita, N. Hosogane, K. Horiuchi, T. Kimura, Y. Okada, T. Saito, H. Kawaguchi, T. Kikuchi, Morio Matsumoto, Y. Toyama, K. Chiba

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective: The role of postmenopause on the pathogenesis of cartilage degeneration has been an open question. We assessed cartilage degeneration in estrogen receptor (ER)α null mice and examined the role of glucocorticoid receptor-interacting protein 1 (GRIP1) in the ERα-dependent transcription of a type II collagen gene (col2a1) with special reference to a crosstalk with the transforming growth factor (TGF)-β signaling pathway. Methods: The vertebral cartilaginous endplate from female ERα null mice was subjected to histological analyses. Col2a1 expression of primary chondrocytes (PCs) obtained from ERα null mice after 17β-estradiol (E2) and TGF-β1 stimulation was examined by reverse transcription polymerase chain reaction (RT-PCR). Estrogen response element (ERE) or col2a1 promoter-enhancer luciferase reporter system was used to investigate the crosstalk among ERα, GRIP1, and MKK6. Col2a1 expression and glycosaminoglycan (GAG) content were measured in ATDC5 cells treated with GRIP1 small interfering RNA (siRNA). Results: ERα deficiency clearly accelerated impairment of the vertebral cartilaginous endplate. E2 and TGF-β1 stimulation increased col2a1 expression in PC from wild-type mice, but not that from ERα null mice. The same stimulation increased the col2a1 promoter-enhancer reporter activity, and the elevated activity was decreased by dominant-negative ERα and p38 mitogen-activated protein kinase (MAPK) inhibitor. GRIP1 increased the E2-dependent ERE activation in the presence of ERα and constitutive-active MKK6. GRIP1 siRNA repressed col2a1 expression and GAG production in ATDC5 cells. Conclusions: Crosstalks between ERα/GRIP1 and TGF-β/MKK6/p38 MAPK pathway have protective roles on cartilage metabolism via regulating the extracellular matrices expression. The finding may lead to the development of a novel therapeutic approach for cartilage degeneration.

Original languageEnglish
Pages (from-to)934-941
Number of pages8
JournalOsteoarthritis and Cartilage
Volume18
Issue number7
DOIs
Publication statusPublished - 2010 Jul

Fingerprint

Nuclear Receptor Coactivator 2
Gene expression
Estrogen Receptors
Extracellular Matrix
Proteins
Gene Expression
Transforming Growth Factors
Cartilage
Crosstalk
Response Elements
p38 Mitogen-Activated Protein Kinases
Chondrocytes
Glycosaminoglycans
Small Interfering RNA
Transcription
RNA
Estrogens
Glucocorticoids
Postmenopause
Collagen Type II

Keywords

  • Cartilaginous endplate
  • Chondrocyte
  • Estrogen receptor
  • GRIP1
  • Intervertebral disc
  • MKK6

ASJC Scopus subject areas

  • Biomedical Engineering
  • Orthopedics and Sports Medicine
  • Rheumatology

Cite this

GRIP1 enhances estrogen receptor α-dependent extracellular matrix gene expression in chondrogenic cells. / Kato, M.; Takaishi, H.; Yoda, Masaki; Tohmonda, T.; Takito, J.; Fujita, Nobuyuki; Hosogane, N.; Horiuchi, K.; Kimura, T.; Okada, Y.; Saito, T.; Kawaguchi, H.; Kikuchi, T.; Matsumoto, Morio; Toyama, Y.; Chiba, K.

In: Osteoarthritis and Cartilage, Vol. 18, No. 7, 07.2010, p. 934-941.

Research output: Contribution to journalArticle

Kato, M, Takaishi, H, Yoda, M, Tohmonda, T, Takito, J, Fujita, N, Hosogane, N, Horiuchi, K, Kimura, T, Okada, Y, Saito, T, Kawaguchi, H, Kikuchi, T, Matsumoto, M, Toyama, Y & Chiba, K 2010, 'GRIP1 enhances estrogen receptor α-dependent extracellular matrix gene expression in chondrogenic cells', Osteoarthritis and Cartilage, vol. 18, no. 7, pp. 934-941. https://doi.org/10.1016/j.joca.2010.03.008
Kato, M. ; Takaishi, H. ; Yoda, Masaki ; Tohmonda, T. ; Takito, J. ; Fujita, Nobuyuki ; Hosogane, N. ; Horiuchi, K. ; Kimura, T. ; Okada, Y. ; Saito, T. ; Kawaguchi, H. ; Kikuchi, T. ; Matsumoto, Morio ; Toyama, Y. ; Chiba, K. / GRIP1 enhances estrogen receptor α-dependent extracellular matrix gene expression in chondrogenic cells. In: Osteoarthritis and Cartilage. 2010 ; Vol. 18, No. 7. pp. 934-941.
@article{ac150014eb6e46d49d9c05fc92672977,
title = "GRIP1 enhances estrogen receptor α-dependent extracellular matrix gene expression in chondrogenic cells",
abstract = "Objective: The role of postmenopause on the pathogenesis of cartilage degeneration has been an open question. We assessed cartilage degeneration in estrogen receptor (ER)α null mice and examined the role of glucocorticoid receptor-interacting protein 1 (GRIP1) in the ERα-dependent transcription of a type II collagen gene (col2a1) with special reference to a crosstalk with the transforming growth factor (TGF)-β signaling pathway. Methods: The vertebral cartilaginous endplate from female ERα null mice was subjected to histological analyses. Col2a1 expression of primary chondrocytes (PCs) obtained from ERα null mice after 17β-estradiol (E2) and TGF-β1 stimulation was examined by reverse transcription polymerase chain reaction (RT-PCR). Estrogen response element (ERE) or col2a1 promoter-enhancer luciferase reporter system was used to investigate the crosstalk among ERα, GRIP1, and MKK6. Col2a1 expression and glycosaminoglycan (GAG) content were measured in ATDC5 cells treated with GRIP1 small interfering RNA (siRNA). Results: ERα deficiency clearly accelerated impairment of the vertebral cartilaginous endplate. E2 and TGF-β1 stimulation increased col2a1 expression in PC from wild-type mice, but not that from ERα null mice. The same stimulation increased the col2a1 promoter-enhancer reporter activity, and the elevated activity was decreased by dominant-negative ERα and p38 mitogen-activated protein kinase (MAPK) inhibitor. GRIP1 increased the E2-dependent ERE activation in the presence of ERα and constitutive-active MKK6. GRIP1 siRNA repressed col2a1 expression and GAG production in ATDC5 cells. Conclusions: Crosstalks between ERα/GRIP1 and TGF-β/MKK6/p38 MAPK pathway have protective roles on cartilage metabolism via regulating the extracellular matrices expression. The finding may lead to the development of a novel therapeutic approach for cartilage degeneration.",
keywords = "Cartilaginous endplate, Chondrocyte, Estrogen receptor, GRIP1, Intervertebral disc, MKK6",
author = "M. Kato and H. Takaishi and Masaki Yoda and T. Tohmonda and J. Takito and Nobuyuki Fujita and N. Hosogane and K. Horiuchi and T. Kimura and Y. Okada and T. Saito and H. Kawaguchi and T. Kikuchi and Morio Matsumoto and Y. Toyama and K. Chiba",
year = "2010",
month = "7",
doi = "10.1016/j.joca.2010.03.008",
language = "English",
volume = "18",
pages = "934--941",
journal = "Osteoarthritis and Cartilage",
issn = "1063-4584",
publisher = "W.B. Saunders Ltd",
number = "7",

}

TY - JOUR

T1 - GRIP1 enhances estrogen receptor α-dependent extracellular matrix gene expression in chondrogenic cells

AU - Kato, M.

AU - Takaishi, H.

AU - Yoda, Masaki

AU - Tohmonda, T.

AU - Takito, J.

AU - Fujita, Nobuyuki

AU - Hosogane, N.

AU - Horiuchi, K.

AU - Kimura, T.

AU - Okada, Y.

AU - Saito, T.

AU - Kawaguchi, H.

AU - Kikuchi, T.

AU - Matsumoto, Morio

AU - Toyama, Y.

AU - Chiba, K.

PY - 2010/7

Y1 - 2010/7

N2 - Objective: The role of postmenopause on the pathogenesis of cartilage degeneration has been an open question. We assessed cartilage degeneration in estrogen receptor (ER)α null mice and examined the role of glucocorticoid receptor-interacting protein 1 (GRIP1) in the ERα-dependent transcription of a type II collagen gene (col2a1) with special reference to a crosstalk with the transforming growth factor (TGF)-β signaling pathway. Methods: The vertebral cartilaginous endplate from female ERα null mice was subjected to histological analyses. Col2a1 expression of primary chondrocytes (PCs) obtained from ERα null mice after 17β-estradiol (E2) and TGF-β1 stimulation was examined by reverse transcription polymerase chain reaction (RT-PCR). Estrogen response element (ERE) or col2a1 promoter-enhancer luciferase reporter system was used to investigate the crosstalk among ERα, GRIP1, and MKK6. Col2a1 expression and glycosaminoglycan (GAG) content were measured in ATDC5 cells treated with GRIP1 small interfering RNA (siRNA). Results: ERα deficiency clearly accelerated impairment of the vertebral cartilaginous endplate. E2 and TGF-β1 stimulation increased col2a1 expression in PC from wild-type mice, but not that from ERα null mice. The same stimulation increased the col2a1 promoter-enhancer reporter activity, and the elevated activity was decreased by dominant-negative ERα and p38 mitogen-activated protein kinase (MAPK) inhibitor. GRIP1 increased the E2-dependent ERE activation in the presence of ERα and constitutive-active MKK6. GRIP1 siRNA repressed col2a1 expression and GAG production in ATDC5 cells. Conclusions: Crosstalks between ERα/GRIP1 and TGF-β/MKK6/p38 MAPK pathway have protective roles on cartilage metabolism via regulating the extracellular matrices expression. The finding may lead to the development of a novel therapeutic approach for cartilage degeneration.

AB - Objective: The role of postmenopause on the pathogenesis of cartilage degeneration has been an open question. We assessed cartilage degeneration in estrogen receptor (ER)α null mice and examined the role of glucocorticoid receptor-interacting protein 1 (GRIP1) in the ERα-dependent transcription of a type II collagen gene (col2a1) with special reference to a crosstalk with the transforming growth factor (TGF)-β signaling pathway. Methods: The vertebral cartilaginous endplate from female ERα null mice was subjected to histological analyses. Col2a1 expression of primary chondrocytes (PCs) obtained from ERα null mice after 17β-estradiol (E2) and TGF-β1 stimulation was examined by reverse transcription polymerase chain reaction (RT-PCR). Estrogen response element (ERE) or col2a1 promoter-enhancer luciferase reporter system was used to investigate the crosstalk among ERα, GRIP1, and MKK6. Col2a1 expression and glycosaminoglycan (GAG) content were measured in ATDC5 cells treated with GRIP1 small interfering RNA (siRNA). Results: ERα deficiency clearly accelerated impairment of the vertebral cartilaginous endplate. E2 and TGF-β1 stimulation increased col2a1 expression in PC from wild-type mice, but not that from ERα null mice. The same stimulation increased the col2a1 promoter-enhancer reporter activity, and the elevated activity was decreased by dominant-negative ERα and p38 mitogen-activated protein kinase (MAPK) inhibitor. GRIP1 increased the E2-dependent ERE activation in the presence of ERα and constitutive-active MKK6. GRIP1 siRNA repressed col2a1 expression and GAG production in ATDC5 cells. Conclusions: Crosstalks between ERα/GRIP1 and TGF-β/MKK6/p38 MAPK pathway have protective roles on cartilage metabolism via regulating the extracellular matrices expression. The finding may lead to the development of a novel therapeutic approach for cartilage degeneration.

KW - Cartilaginous endplate

KW - Chondrocyte

KW - Estrogen receptor

KW - GRIP1

KW - Intervertebral disc

KW - MKK6

UR - http://www.scopus.com/inward/record.url?scp=77954215305&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954215305&partnerID=8YFLogxK

U2 - 10.1016/j.joca.2010.03.008

DO - 10.1016/j.joca.2010.03.008

M3 - Article

C2 - 20346402

AN - SCOPUS:77954215305

VL - 18

SP - 934

EP - 941

JO - Osteoarthritis and Cartilage

JF - Osteoarthritis and Cartilage

SN - 1063-4584

IS - 7

ER -