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Hypoxia‐Mediated Mitochondrial Stress in RAW264.7 Cells Induces Osteoclast‐Like TRAP‐Positive Cells
Author(s) -
SRINIVASAN SATISH,
AVADHANI NARAYAN G.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1402.067
Subject(s) - microbiology and biotechnology , chemistry , reactive oxygen species , hypoxia (environmental) , calcineurin , oxidative stress , medicine , biology , biochemistry , oxygen , transplantation , organic chemistry
: Previously we showed that mitochondrial dysfunction induced by mitochondrial DNA depletion or treatment with electron transport chain inhibitors triggers a stress signaling involving activation of calcineurin and Ca 2+ ‐responsive factors. In this study we show that exposure of RAW 264.7 cells to hypoxia, causing increased reactive oxygen species (ROS) production and disruption of mitochondrial transmembrane potential, also induced a similar stress signaling. Hypoxia caused increased [Ca 2+ ]c, activation of cytosolic calcineurin and induced expression of Ryanodine Receptor 2 (RyR2) gene. Prolonged hypoxia (5% O 2 for 5–6 days) also induced the expression of calcitonin receptor at high levels, and those of cathepsin K, and tartarate‐resistant alkaline phosphatase (TRAP) at low‐moderate levels in macrophage cells. Addition of RANKL had an additive effect suggesting different mechanisms of activation. Consistent with this possibility, prolonged hypoxia induced the formation of TRAP‐positive osteoclast‐like cells suggesting the occurrence of an autocrine mechanism for osteoclastogenesis.