LOX-1 expressed in cultured rat chondrocytes mediates oxidized LDL-induced cell death - Possible role of dephosphorylation of Akt

Takefumi Nakagawa, Tadashi Yasuda, Hajime Hoshikawa, Makoto Shimizu, Takumi Kakinuma, Mingyi Chen, Tomoh Masaki, Takashi Nakamura, Tatsuya Sawamura

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The oxidative changes of lipids in cartilage proceed with ageing and with the grade of osteoarthritis. To clarify the role of oxidatively modified lipids in articular cartilage in osteoarthritis, here, we investigated lectin-like oxidized LDL receptor (LOX-1) in rat cultured articular chondrocytes. LOX-1 expression was detectable in basal culture condition and enhanced by the treatment of oxidized LDL and interleukin-1β. DiI-labeled oxidized LDL was bound and ingested by chondrocytes via LOX-1. Oxidized LDL dose-dependently reduced chondrocyte viability, inducing non-apoptotic cell death, which was again suppressed by anti-LOX-1 antibody treatment. Oxidized LDL reduced the amount of phosphorylated Akt, a substrate of PI3 kinase via LOX-1. Consistently, the PI3 kinase inhibitor, LY294002, decreased cell viability dose-dependently, and the PI3 kinase activator, IGF-I, reversed the effect of oxidized LDL on the cell death. LOX-1 might be involved in the pathogenesis of osteoarthritis, inducing chondrocyte death through PI3 kinase/Akt pathway.

Original languageEnglish (US)
Pages (from-to)91-97
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume299
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

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Cell death
Chondrocytes
Rats
Cell Death
Phosphatidylinositol 3-Kinases
Osteoarthritis
Cartilage
Oxidized LDL Receptors
Lipids
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Articular Cartilage
Insulin-Like Growth Factor I
Interleukin-1
LDL Lipoproteins
Lectins
Cell Survival
Joints
Aging of materials
Cells
oxidized low density lipoprotein

Keywords

  • Cell death
  • Chondrocytes
  • LOX-1
  • Osteoarthrtis
  • Oxidized LDL
  • Phosphatidylinositol 3-kinase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

LOX-1 expressed in cultured rat chondrocytes mediates oxidized LDL-induced cell death - Possible role of dephosphorylation of Akt. / Nakagawa, Takefumi; Yasuda, Tadashi; Hoshikawa, Hajime; Shimizu, Makoto; Kakinuma, Takumi; Chen, Mingyi; Masaki, Tomoh; Nakamura, Takashi; Sawamura, Tatsuya.

In: Biochemical and Biophysical Research Communications, Vol. 299, No. 1, 2002, p. 91-97.

Research output: Contribution to journalArticle

Nakagawa, Takefumi ; Yasuda, Tadashi ; Hoshikawa, Hajime ; Shimizu, Makoto ; Kakinuma, Takumi ; Chen, Mingyi ; Masaki, Tomoh ; Nakamura, Takashi ; Sawamura, Tatsuya. / LOX-1 expressed in cultured rat chondrocytes mediates oxidized LDL-induced cell death - Possible role of dephosphorylation of Akt. In: Biochemical and Biophysical Research Communications. 2002 ; Vol. 299, No. 1. pp. 91-97.
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