Ctgf/hcs24 induces chondrocyte differentiation through a p38 mitogen-activated protein kinase (p38mapk), and proliferation through a p44/42 mapk/extracellular-signal regulated kinase (erk)

Gen Yosimichi, Tohru Nakanishi, Takashi Nishida, Takako Hattori, Teruko Takano-Yamamoto, Masaharu Takigawa

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126 Citations (Scopus)

Abstract

Connective tissue growth factor/hypertrophic chondrocyte specific gene product 24 (CTGF/Hcs24) promotes proliferation and differentiation of chondrocytes in culture. We investigated the roles of two major types of mitogen activated protein kinase (MAPK) in the promotion of proliferation and differentiation by CTGF/Hcs24. Here we report the effects of the MAPKK/MEK 1/2 inhibitor, PD098059, and p38 MAPK inhibitor, SB203580, in a human chondro-sarcoma-derived chondrocytic cell line (HCS-2/8) and rabbit growth cartilage (RGC) cells treated with CTGF/Hcs24. In the proliferation phase, CTGF/Hcs24 induced a ≃ fivefold increase in the phosphorylation of p44/42 MAPK/ERK and a ≃ twofold increase in that of p38 MAPK in an in vivo kinase assay. These inhibitors of MAPKK and MAPK suppressed phosphorylation of ets-like gene-1 (Elk-1) and nuclear activating transcription factor-2 (Atf-2) induced by CTGF/Hcs24 in a dose-dependent manner, respectively. Western blot analysis showed that phosphorylation of ERK was induced from 30 to 60 min and phosphorylation of p38 MAPK from 10 to 15 min after the addition of CTGF/Hcs24 in confluence HCS-2/8 cells. PD098059 suppressed the DNA synthesis of HCS-2/8 cells and RGC cells, while SB203580 did not. On the other hand, the p38 MAPK inhibitor, SB203580, completely inhibited the CTGF/Hcs24-induced synthesis of proteoglycans in HCS-2/8 cells and RGC cells but the MEK1/2 inhibitor, PD098059, did not. These results suggest that ERK mediates the CTGF/Hcs24-induced proliferation of chondrocytes, and that p38 MAPK mediates the CTGF/Hcs24-induced differentiation of chondrocytes.

Original languageEnglish
Pages (from-to)6058-6065
Number of pages8
JournalEuropean Journal of Biochemistry
Volume268
Issue number23
DOIs
Publication statusPublished - 2001

Fingerprint

Connective Tissue Growth Factor
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases
Chondrocytes
Genes
Phosphorylation
Mitogen-Activated Protein Kinase Kinases
Cartilage
Mitogen-Activated Protein Kinases
Protein Kinase Inhibitors
Mitogen-Activated Protein Kinase 10
Rabbits
Activating Transcription Factor 2
Growth
Proteoglycans
Assays
Phosphotransferases
Sarcoma
Cells
Western Blotting

Keywords

  • Chondrocyte
  • Connective tissue growth factor
  • Hypertrophic chondrocyte specific gene product (CTGF/Hcs24)
  • MAPK
  • MAPK inhibitor
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{1497d65d813947558059b69552fd08e3,
title = "Ctgf/hcs24 induces chondrocyte differentiation through a p38 mitogen-activated protein kinase (p38mapk), and proliferation through a p44/42 mapk/extracellular-signal regulated kinase (erk)",
abstract = "Connective tissue growth factor/hypertrophic chondrocyte specific gene product 24 (CTGF/Hcs24) promotes proliferation and differentiation of chondrocytes in culture. We investigated the roles of two major types of mitogen activated protein kinase (MAPK) in the promotion of proliferation and differentiation by CTGF/Hcs24. Here we report the effects of the MAPKK/MEK 1/2 inhibitor, PD098059, and p38 MAPK inhibitor, SB203580, in a human chondro-sarcoma-derived chondrocytic cell line (HCS-2/8) and rabbit growth cartilage (RGC) cells treated with CTGF/Hcs24. In the proliferation phase, CTGF/Hcs24 induced a ≃ fivefold increase in the phosphorylation of p44/42 MAPK/ERK and a ≃ twofold increase in that of p38 MAPK in an in vivo kinase assay. These inhibitors of MAPKK and MAPK suppressed phosphorylation of ets-like gene-1 (Elk-1) and nuclear activating transcription factor-2 (Atf-2) induced by CTGF/Hcs24 in a dose-dependent manner, respectively. Western blot analysis showed that phosphorylation of ERK was induced from 30 to 60 min and phosphorylation of p38 MAPK from 10 to 15 min after the addition of CTGF/Hcs24 in confluence HCS-2/8 cells. PD098059 suppressed the DNA synthesis of HCS-2/8 cells and RGC cells, while SB203580 did not. On the other hand, the p38 MAPK inhibitor, SB203580, completely inhibited the CTGF/Hcs24-induced synthesis of proteoglycans in HCS-2/8 cells and RGC cells but the MEK1/2 inhibitor, PD098059, did not. These results suggest that ERK mediates the CTGF/Hcs24-induced proliferation of chondrocytes, and that p38 MAPK mediates the CTGF/Hcs24-induced differentiation of chondrocytes.",
keywords = "Chondrocyte, Connective tissue growth factor, Hypertrophic chondrocyte specific gene product (CTGF/Hcs24), MAPK, MAPK inhibitor, Signal transduction",
author = "Gen Yosimichi and Tohru Nakanishi and Takashi Nishida and Takako Hattori and Teruko Takano-Yamamoto and Masaharu Takigawa",
year = "2001",
doi = "10.1046/j.0014-2956.2001.02553.x",
language = "English",
volume = "268",
pages = "6058--6065",
journal = "FEBS Journal",
issn = "1742-464X",
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T1 - Ctgf/hcs24 induces chondrocyte differentiation through a p38 mitogen-activated protein kinase (p38mapk), and proliferation through a p44/42 mapk/extracellular-signal regulated kinase (erk)

AU - Yosimichi, Gen

AU - Nakanishi, Tohru

AU - Nishida, Takashi

AU - Hattori, Takako

AU - Takano-Yamamoto, Teruko

AU - Takigawa, Masaharu

PY - 2001

Y1 - 2001

N2 - Connective tissue growth factor/hypertrophic chondrocyte specific gene product 24 (CTGF/Hcs24) promotes proliferation and differentiation of chondrocytes in culture. We investigated the roles of two major types of mitogen activated protein kinase (MAPK) in the promotion of proliferation and differentiation by CTGF/Hcs24. Here we report the effects of the MAPKK/MEK 1/2 inhibitor, PD098059, and p38 MAPK inhibitor, SB203580, in a human chondro-sarcoma-derived chondrocytic cell line (HCS-2/8) and rabbit growth cartilage (RGC) cells treated with CTGF/Hcs24. In the proliferation phase, CTGF/Hcs24 induced a ≃ fivefold increase in the phosphorylation of p44/42 MAPK/ERK and a ≃ twofold increase in that of p38 MAPK in an in vivo kinase assay. These inhibitors of MAPKK and MAPK suppressed phosphorylation of ets-like gene-1 (Elk-1) and nuclear activating transcription factor-2 (Atf-2) induced by CTGF/Hcs24 in a dose-dependent manner, respectively. Western blot analysis showed that phosphorylation of ERK was induced from 30 to 60 min and phosphorylation of p38 MAPK from 10 to 15 min after the addition of CTGF/Hcs24 in confluence HCS-2/8 cells. PD098059 suppressed the DNA synthesis of HCS-2/8 cells and RGC cells, while SB203580 did not. On the other hand, the p38 MAPK inhibitor, SB203580, completely inhibited the CTGF/Hcs24-induced synthesis of proteoglycans in HCS-2/8 cells and RGC cells but the MEK1/2 inhibitor, PD098059, did not. These results suggest that ERK mediates the CTGF/Hcs24-induced proliferation of chondrocytes, and that p38 MAPK mediates the CTGF/Hcs24-induced differentiation of chondrocytes.

AB - Connective tissue growth factor/hypertrophic chondrocyte specific gene product 24 (CTGF/Hcs24) promotes proliferation and differentiation of chondrocytes in culture. We investigated the roles of two major types of mitogen activated protein kinase (MAPK) in the promotion of proliferation and differentiation by CTGF/Hcs24. Here we report the effects of the MAPKK/MEK 1/2 inhibitor, PD098059, and p38 MAPK inhibitor, SB203580, in a human chondro-sarcoma-derived chondrocytic cell line (HCS-2/8) and rabbit growth cartilage (RGC) cells treated with CTGF/Hcs24. In the proliferation phase, CTGF/Hcs24 induced a ≃ fivefold increase in the phosphorylation of p44/42 MAPK/ERK and a ≃ twofold increase in that of p38 MAPK in an in vivo kinase assay. These inhibitors of MAPKK and MAPK suppressed phosphorylation of ets-like gene-1 (Elk-1) and nuclear activating transcription factor-2 (Atf-2) induced by CTGF/Hcs24 in a dose-dependent manner, respectively. Western blot analysis showed that phosphorylation of ERK was induced from 30 to 60 min and phosphorylation of p38 MAPK from 10 to 15 min after the addition of CTGF/Hcs24 in confluence HCS-2/8 cells. PD098059 suppressed the DNA synthesis of HCS-2/8 cells and RGC cells, while SB203580 did not. On the other hand, the p38 MAPK inhibitor, SB203580, completely inhibited the CTGF/Hcs24-induced synthesis of proteoglycans in HCS-2/8 cells and RGC cells but the MEK1/2 inhibitor, PD098059, did not. These results suggest that ERK mediates the CTGF/Hcs24-induced proliferation of chondrocytes, and that p38 MAPK mediates the CTGF/Hcs24-induced differentiation of chondrocytes.

KW - Chondrocyte

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KW - Hypertrophic chondrocyte specific gene product (CTGF/Hcs24)

KW - MAPK

KW - MAPK inhibitor

KW - Signal transduction

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