Role of Rho small GTPases in meniscus cells

Tomoko Kanazawa, Takayuki Furumatsu, Emi Matsumoto-Ogawa, Ami Maehara, Toshihumi Ozaki

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We previously reported that mechanical stretch regulates Sry-type HMG box (SOX) 9-dependent α1(II) collagen (COL2A1) expression in inner meniscus cells. This study examined the role of the small Rho guanosine 5' triphosphatase Rac1 and Rho-associated kinase (ROCK) in the regulation of stretch-induced SOX9 gene expression in cultured human inner meniscus cells. COL2A1 and SOX9 gene expression was assessed by real-time PCR after application of uni-axial cyclic tensile strain (CTS) in the presence or absence of ROCK and Rac1 inhibitors. The subcellular localization of SOX9 and the Rac1 effector cyclic AMP response element-binding protein (CREB), the phosphorylation state of SOX9, Rac1 activation, and the binding of CREB to the SOX9 promoter were assessed. CTS increased the expression of COL2A1 and SOX9, which was suppressed by inhibition of Rac1. ROCK inhibition enhanced COL2A1 and SOX9 gene expression in the absence of CTS. CTS stimulated the nuclear translocation and phosphorylation of SOX9, and increased Rac1 activation. CTS also increased the binding of CREB to the SOX9 promoter. The results suggest that mechanical stretch-dependent upregulation of SOX9 by CREB in inner meniscus cells depends on the antagonistic activities of ROCK and Rac1.

Original languageEnglish
Pages (from-to)1479-1486
Number of pages8
JournalJournal of Orthopaedic Research
Volume32
Issue number11
DOIs
Publication statusPublished - Nov 1 2014

Fingerprint

Cyclic AMP Response Element-Binding Protein
rho-Associated Kinases
rho GTP-Binding Proteins
Monomeric GTP-Binding Proteins
Gene Expression
Phosphorylation
Guanosine
Real-Time Polymerase Chain Reaction
Up-Regulation
Collagen
Meniscus

Keywords

  • CREB
  • Mechanical stretch
  • Meniscus
  • Rac1
  • ROCK
  • SOX9

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Medicine(all)

Cite this

Role of Rho small GTPases in meniscus cells. / Kanazawa, Tomoko; Furumatsu, Takayuki; Matsumoto-Ogawa, Emi; Maehara, Ami; Ozaki, Toshihumi.

In: Journal of Orthopaedic Research, Vol. 32, No. 11, 01.11.2014, p. 1479-1486.

Research output: Contribution to journalArticle

Kanazawa, T, Furumatsu, T, Matsumoto-Ogawa, E, Maehara, A & Ozaki, T 2014, 'Role of Rho small GTPases in meniscus cells', Journal of Orthopaedic Research, vol. 32, no. 11, pp. 1479-1486. https://doi.org/10.1002/jor.22703
Kanazawa, Tomoko ; Furumatsu, Takayuki ; Matsumoto-Ogawa, Emi ; Maehara, Ami ; Ozaki, Toshihumi. / Role of Rho small GTPases in meniscus cells. In: Journal of Orthopaedic Research. 2014 ; Vol. 32, No. 11. pp. 1479-1486.
@article{26f9df4584ab4caea3906bae4de1ba71,
title = "Role of Rho small GTPases in meniscus cells",
abstract = "We previously reported that mechanical stretch regulates Sry-type HMG box (SOX) 9-dependent α1(II) collagen (COL2A1) expression in inner meniscus cells. This study examined the role of the small Rho guanosine 5' triphosphatase Rac1 and Rho-associated kinase (ROCK) in the regulation of stretch-induced SOX9 gene expression in cultured human inner meniscus cells. COL2A1 and SOX9 gene expression was assessed by real-time PCR after application of uni-axial cyclic tensile strain (CTS) in the presence or absence of ROCK and Rac1 inhibitors. The subcellular localization of SOX9 and the Rac1 effector cyclic AMP response element-binding protein (CREB), the phosphorylation state of SOX9, Rac1 activation, and the binding of CREB to the SOX9 promoter were assessed. CTS increased the expression of COL2A1 and SOX9, which was suppressed by inhibition of Rac1. ROCK inhibition enhanced COL2A1 and SOX9 gene expression in the absence of CTS. CTS stimulated the nuclear translocation and phosphorylation of SOX9, and increased Rac1 activation. CTS also increased the binding of CREB to the SOX9 promoter. The results suggest that mechanical stretch-dependent upregulation of SOX9 by CREB in inner meniscus cells depends on the antagonistic activities of ROCK and Rac1.",
keywords = "CREB, Mechanical stretch, Meniscus, Rac1, ROCK, SOX9",
author = "Tomoko Kanazawa and Takayuki Furumatsu and Emi Matsumoto-Ogawa and Ami Maehara and Toshihumi Ozaki",
year = "2014",
month = "11",
day = "1",
doi = "10.1002/jor.22703",
language = "English",
volume = "32",
pages = "1479--1486",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "11",

}

TY - JOUR

T1 - Role of Rho small GTPases in meniscus cells

AU - Kanazawa, Tomoko

AU - Furumatsu, Takayuki

AU - Matsumoto-Ogawa, Emi

AU - Maehara, Ami

AU - Ozaki, Toshihumi

PY - 2014/11/1

Y1 - 2014/11/1

N2 - We previously reported that mechanical stretch regulates Sry-type HMG box (SOX) 9-dependent α1(II) collagen (COL2A1) expression in inner meniscus cells. This study examined the role of the small Rho guanosine 5' triphosphatase Rac1 and Rho-associated kinase (ROCK) in the regulation of stretch-induced SOX9 gene expression in cultured human inner meniscus cells. COL2A1 and SOX9 gene expression was assessed by real-time PCR after application of uni-axial cyclic tensile strain (CTS) in the presence or absence of ROCK and Rac1 inhibitors. The subcellular localization of SOX9 and the Rac1 effector cyclic AMP response element-binding protein (CREB), the phosphorylation state of SOX9, Rac1 activation, and the binding of CREB to the SOX9 promoter were assessed. CTS increased the expression of COL2A1 and SOX9, which was suppressed by inhibition of Rac1. ROCK inhibition enhanced COL2A1 and SOX9 gene expression in the absence of CTS. CTS stimulated the nuclear translocation and phosphorylation of SOX9, and increased Rac1 activation. CTS also increased the binding of CREB to the SOX9 promoter. The results suggest that mechanical stretch-dependent upregulation of SOX9 by CREB in inner meniscus cells depends on the antagonistic activities of ROCK and Rac1.

AB - We previously reported that mechanical stretch regulates Sry-type HMG box (SOX) 9-dependent α1(II) collagen (COL2A1) expression in inner meniscus cells. This study examined the role of the small Rho guanosine 5' triphosphatase Rac1 and Rho-associated kinase (ROCK) in the regulation of stretch-induced SOX9 gene expression in cultured human inner meniscus cells. COL2A1 and SOX9 gene expression was assessed by real-time PCR after application of uni-axial cyclic tensile strain (CTS) in the presence or absence of ROCK and Rac1 inhibitors. The subcellular localization of SOX9 and the Rac1 effector cyclic AMP response element-binding protein (CREB), the phosphorylation state of SOX9, Rac1 activation, and the binding of CREB to the SOX9 promoter were assessed. CTS increased the expression of COL2A1 and SOX9, which was suppressed by inhibition of Rac1. ROCK inhibition enhanced COL2A1 and SOX9 gene expression in the absence of CTS. CTS stimulated the nuclear translocation and phosphorylation of SOX9, and increased Rac1 activation. CTS also increased the binding of CREB to the SOX9 promoter. The results suggest that mechanical stretch-dependent upregulation of SOX9 by CREB in inner meniscus cells depends on the antagonistic activities of ROCK and Rac1.

KW - CREB

KW - Mechanical stretch

KW - Meniscus

KW - Rac1

KW - ROCK

KW - SOX9

UR - http://www.scopus.com/inward/record.url?scp=84909989469&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84909989469&partnerID=8YFLogxK

U2 - 10.1002/jor.22703

DO - 10.1002/jor.22703

M3 - Article

VL - 32

SP - 1479

EP - 1486

JO - Journal of Orthopaedic Research

JF - Journal of Orthopaedic Research

SN - 0736-0266

IS - 11

ER -