ADAMTS-9 is synergistically induced by interleukin-1β and tumor necrosis factor α in OUMS-27 chondrosarcoma cells and in human chondrocytes

Kadir Demircan, Satoshi Hirohata, Keiichiro Nishida, Omer F. Hatipoglu, Toshitaka Oohashi, Tomoko Yonezawa, Suneel S. Apte, Yoshifumi Ninomiya

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Abstract

Objective. To compare induction of the aggrecanases (ADAMTS-1, ADAMTS-4, ADAMTS-5, ADAMTS-8, ADAMTS-9, and ADAMTS-15) by interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) in chondrocyte-like OUMS-27 cells and human chondrocytes, and to determine the mechanism of induction of the most responsive aggrecanase gene. Methods. OUMS-27 cells were stimulated for different periods of time and with various concentrations of IL-1β and/or TNFα. Human chondrocytes obtained from osteoarthritic joints and human skin fibroblasts were also stimulated with IL-1β and/or TNFα. Total RNA was extracted, reverse transcribed, and analyzed by quantitative real-time polymerase chain reaction and Northern blotting. ADAMTS-9 protein was examined by Western blotting, and the role of the MAPK signaling pathway for ADAMTS9 induction in IL-1β-stimulated OUMS-27 cells was investigated. Results. IL-1β increased messenger RNA (mRNA) levels of ADAMTS4, ADAMTS5, and ADAMTS9 but not ADAMTS1 and ADAMTS8. The fold increase for ADAMTS9 mRNA was greater than that for mRNA of the other aggrecanase genes. The increase of ADAMTS9 mRNA by IL-1β stimulation was greater in chondrocytes than in fibroblasts. The combination of IL-1β and TNFα had a synergistic effect, resulting in a considerable elevation in the level of ADAMTS9 mRNA. ADAMTS-9 protein was also induced in IL-1β-stimulated OUMS-27 cells. The MAPK inhibitors SB203580 and PD98059 decreased ADAMTS9 upregulation in OUMS-27 cells. Conclusion. ADAMTS9 is an IL-1β- and TNFα-inducible gene that appears to be more responsive to these proinflammatory cytokines than are other aggrecanase genes. Furthermore, these cytokines had a synergistic effect on ADAMTS9. Together with the known ability of ADAMTS-9 to proteolytically degrade aggrecan and its potential to cleave other cartilage molecules, the data suggest that ADAMTS-9 may have a pathologic role in arthritis.

Original languageEnglish
Pages (from-to)1451-1460
Number of pages10
JournalArthritis and Rheumatism
Volume52
Issue number5
DOIs
Publication statusPublished - May 2005

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Chondrosarcoma
Chondrocytes
Interleukin-1
Tumor Necrosis Factor-alpha
Messenger RNA
Genes
Fibroblasts
Cytokines
Aggrecans
Northern Blotting
Arthritis
Cartilage
Real-Time Polymerase Chain Reaction
Up-Regulation
Joints
Western Blotting
RNA
Skin

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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ADAMTS-9 is synergistically induced by interleukin-1β and tumor necrosis factor α in OUMS-27 chondrosarcoma cells and in human chondrocytes. / Demircan, Kadir; Hirohata, Satoshi; Nishida, Keiichiro; Hatipoglu, Omer F.; Oohashi, Toshitaka; Yonezawa, Tomoko; Apte, Suneel S.; Ninomiya, Yoshifumi.

In: Arthritis and Rheumatism, Vol. 52, No. 5, 05.2005, p. 1451-1460.

Research output: Contribution to journalArticle

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title = "ADAMTS-9 is synergistically induced by interleukin-1β and tumor necrosis factor α in OUMS-27 chondrosarcoma cells and in human chondrocytes",
abstract = "Objective. To compare induction of the aggrecanases (ADAMTS-1, ADAMTS-4, ADAMTS-5, ADAMTS-8, ADAMTS-9, and ADAMTS-15) by interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) in chondrocyte-like OUMS-27 cells and human chondrocytes, and to determine the mechanism of induction of the most responsive aggrecanase gene. Methods. OUMS-27 cells were stimulated for different periods of time and with various concentrations of IL-1β and/or TNFα. Human chondrocytes obtained from osteoarthritic joints and human skin fibroblasts were also stimulated with IL-1β and/or TNFα. Total RNA was extracted, reverse transcribed, and analyzed by quantitative real-time polymerase chain reaction and Northern blotting. ADAMTS-9 protein was examined by Western blotting, and the role of the MAPK signaling pathway for ADAMTS9 induction in IL-1β-stimulated OUMS-27 cells was investigated. Results. IL-1β increased messenger RNA (mRNA) levels of ADAMTS4, ADAMTS5, and ADAMTS9 but not ADAMTS1 and ADAMTS8. The fold increase for ADAMTS9 mRNA was greater than that for mRNA of the other aggrecanase genes. The increase of ADAMTS9 mRNA by IL-1β stimulation was greater in chondrocytes than in fibroblasts. The combination of IL-1β and TNFα had a synergistic effect, resulting in a considerable elevation in the level of ADAMTS9 mRNA. ADAMTS-9 protein was also induced in IL-1β-stimulated OUMS-27 cells. The MAPK inhibitors SB203580 and PD98059 decreased ADAMTS9 upregulation in OUMS-27 cells. Conclusion. ADAMTS9 is an IL-1β- and TNFα-inducible gene that appears to be more responsive to these proinflammatory cytokines than are other aggrecanase genes. Furthermore, these cytokines had a synergistic effect on ADAMTS9. Together with the known ability of ADAMTS-9 to proteolytically degrade aggrecan and its potential to cleave other cartilage molecules, the data suggest that ADAMTS-9 may have a pathologic role in arthritis.",
author = "Kadir Demircan and Satoshi Hirohata and Keiichiro Nishida and Hatipoglu, {Omer F.} and Toshitaka Oohashi and Tomoko Yonezawa and Apte, {Suneel S.} and Yoshifumi Ninomiya",
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T1 - ADAMTS-9 is synergistically induced by interleukin-1β and tumor necrosis factor α in OUMS-27 chondrosarcoma cells and in human chondrocytes

AU - Demircan, Kadir

AU - Hirohata, Satoshi

AU - Nishida, Keiichiro

AU - Hatipoglu, Omer F.

AU - Oohashi, Toshitaka

AU - Yonezawa, Tomoko

AU - Apte, Suneel S.

AU - Ninomiya, Yoshifumi

PY - 2005/5

Y1 - 2005/5

N2 - Objective. To compare induction of the aggrecanases (ADAMTS-1, ADAMTS-4, ADAMTS-5, ADAMTS-8, ADAMTS-9, and ADAMTS-15) by interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) in chondrocyte-like OUMS-27 cells and human chondrocytes, and to determine the mechanism of induction of the most responsive aggrecanase gene. Methods. OUMS-27 cells were stimulated for different periods of time and with various concentrations of IL-1β and/or TNFα. Human chondrocytes obtained from osteoarthritic joints and human skin fibroblasts were also stimulated with IL-1β and/or TNFα. Total RNA was extracted, reverse transcribed, and analyzed by quantitative real-time polymerase chain reaction and Northern blotting. ADAMTS-9 protein was examined by Western blotting, and the role of the MAPK signaling pathway for ADAMTS9 induction in IL-1β-stimulated OUMS-27 cells was investigated. Results. IL-1β increased messenger RNA (mRNA) levels of ADAMTS4, ADAMTS5, and ADAMTS9 but not ADAMTS1 and ADAMTS8. The fold increase for ADAMTS9 mRNA was greater than that for mRNA of the other aggrecanase genes. The increase of ADAMTS9 mRNA by IL-1β stimulation was greater in chondrocytes than in fibroblasts. The combination of IL-1β and TNFα had a synergistic effect, resulting in a considerable elevation in the level of ADAMTS9 mRNA. ADAMTS-9 protein was also induced in IL-1β-stimulated OUMS-27 cells. The MAPK inhibitors SB203580 and PD98059 decreased ADAMTS9 upregulation in OUMS-27 cells. Conclusion. ADAMTS9 is an IL-1β- and TNFα-inducible gene that appears to be more responsive to these proinflammatory cytokines than are other aggrecanase genes. Furthermore, these cytokines had a synergistic effect on ADAMTS9. Together with the known ability of ADAMTS-9 to proteolytically degrade aggrecan and its potential to cleave other cartilage molecules, the data suggest that ADAMTS-9 may have a pathologic role in arthritis.

AB - Objective. To compare induction of the aggrecanases (ADAMTS-1, ADAMTS-4, ADAMTS-5, ADAMTS-8, ADAMTS-9, and ADAMTS-15) by interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) in chondrocyte-like OUMS-27 cells and human chondrocytes, and to determine the mechanism of induction of the most responsive aggrecanase gene. Methods. OUMS-27 cells were stimulated for different periods of time and with various concentrations of IL-1β and/or TNFα. Human chondrocytes obtained from osteoarthritic joints and human skin fibroblasts were also stimulated with IL-1β and/or TNFα. Total RNA was extracted, reverse transcribed, and analyzed by quantitative real-time polymerase chain reaction and Northern blotting. ADAMTS-9 protein was examined by Western blotting, and the role of the MAPK signaling pathway for ADAMTS9 induction in IL-1β-stimulated OUMS-27 cells was investigated. Results. IL-1β increased messenger RNA (mRNA) levels of ADAMTS4, ADAMTS5, and ADAMTS9 but not ADAMTS1 and ADAMTS8. The fold increase for ADAMTS9 mRNA was greater than that for mRNA of the other aggrecanase genes. The increase of ADAMTS9 mRNA by IL-1β stimulation was greater in chondrocytes than in fibroblasts. The combination of IL-1β and TNFα had a synergistic effect, resulting in a considerable elevation in the level of ADAMTS9 mRNA. ADAMTS-9 protein was also induced in IL-1β-stimulated OUMS-27 cells. The MAPK inhibitors SB203580 and PD98059 decreased ADAMTS9 upregulation in OUMS-27 cells. Conclusion. ADAMTS9 is an IL-1β- and TNFα-inducible gene that appears to be more responsive to these proinflammatory cytokines than are other aggrecanase genes. Furthermore, these cytokines had a synergistic effect on ADAMTS9. Together with the known ability of ADAMTS-9 to proteolytically degrade aggrecan and its potential to cleave other cartilage molecules, the data suggest that ADAMTS-9 may have a pathologic role in arthritis.

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