TY - JOUR
T1 - LOX-1 expressed in cultured rat chondrocytes mediates oxidized LDL-induced cell death - Possible role of dephosphorylation of Akt
AU - Nakagawa, Takefumi
AU - Yasuda, Tadashi
AU - Hoshikawa, Hajime
AU - Shimizu, Makoto
AU - Kakinuma, Takumi
AU - Chen, Mingyi
AU - Masaki, Tomoh
AU - Nakamura, Takashi
AU - Sawamura, Tatsuya
N1 - Funding Information:
This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Ministry of Health, Labor and Welfare of Japan, the Organization for Pharmaceutical Safety and Research, and Mitsubishi Foundations. We thank Tamlyn Thomas for editing the manuscript.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Cell death
KW - Chondrocytes
KW - LOX-1
KW - Osteoarthrtis
KW - Oxidized LDL
KW - Phosphatidylinositol 3-kinase
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U2 - 10.1016/S0006-291X(02)02597-4
DO - 10.1016/S0006-291X(02)02597-4
M3 - Article
C2 - 12435393
AN - SCOPUS:0036436162
SN - 0006-291X
VL - 299
SP - 91
EP - 97
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -