High oxygen tension prolongs the survival of osteoclast precursors via macrophage colony-stimulating factor.
The oxygen tension affects the function, differentiation, and transformation of various cells, including bone cells. In pathological conditions such as rheumatoid arthritis (RA), rapidly destructive arthropathy, and primary or metastatic tumors, severe bone destruction or osteolysis occurs. Abundant blood vessels are often observed around these destructive lesions. At such sites, we have confirmed the increased production of reactive oxygen species (ROS) induced by a high oxygen tension and/or oxidative stress, as well as numerous osteoclasts detectable by immunohistochemistry. These findings suggest that osteoclasts are influenced by the high oxygen tension in pathological bone lesions because the zone around blood vessels has a relatively high oxygen tension. In this study, we investigated the effects of oxygen tension on osteoclastogenesis by culturing human CD14-positive cells (osteoclast precursors) with or without osteoblast-like supporting cells (Saos-4/3 cells) under a normal oxygen tension (20% O(2)) or a high oxygen tension (40% O(2)). A high oxygen tension markedly prolonged the duration of osteoclast precursor formation in the presence of supporting cells, and also markedly and persistently increased the production of macrophage colony stimulating factor (M-CSF) by supporting cells. Furthermore, we found an increase of cells expressing M-CSF and cells positive for tartrate-resistant acid phosphatase (TRAP) in hypervascular destructive bone lesions of RA patients where ROS were also abundant.
Yamasaki
Naomi
N
Department of Orthopedics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Tsuboi
Hideki
H
Hirao
Makoto
M
Nampei
Akihide
A
Yoshikawa
Hideki
H
Hashimoto
Jun
J
D000135:Acid Phosphatase / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D001842:Bone and Bones / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009500:Neutralization Tests; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D010100:Oxygen / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D000071681:Tartrate-Resistant Acid Phosphatase
D000906:Antibodies; D007527:Isoenzymes; D018950:Lipopolysaccharide Receptors; D017382:Reactive Oxygen Species; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D010100:Oxygen