Essential role of macrophage colony-stimulating factor in the osteoclast differentiation supported by stromal cells.
Severe deficiency of osteoclasts, monocytes, and peritoneal macrophages in osteopetrotic (op/op) mutant mice is caused by the absence of functional macrophage colony-stimulating factor (M-CSF). To clarify the role of M-CSF in the osteoclast differentiation, we established a clonal stromal cell line OP6L7 capable of supporting hemopoiesis from newborn op/op mouse calvaria. Although very few macrophages appeared in the cocultures of bone marrow cells and OP6L7 cells, a 50-fold larger number of macrophages was detected in the day 7 cocultures when purified recombinant human M-CSF (rhM-CSF) was exogenously supplied. Tartrate-resistant acid phosphatase (TRACP; a marker enzyme of osteoclasts)-positive cells appeared only when bone marrow cells were cultured in contact with OP6L7 cells and both rhM-CSF and 1 alpha, 25 (OH)2D3 were added. The TRACP-positive cells became multinucleated with increasing time in culture and expressed the c-fms/M-CSF receptor. These results indicate that both contact with stromal cells and M-CSF are requisite for osteoclast differentiation under physiological conditions.
Kodama
H
H
Department of Anatomy, Ohu University School of Dentistry, Koriyama, Japan.
Nose
M
M
Niida
S
S
Yamasaki
A
A
D000135:Acid Phosphatase / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D002117:Calcitriol / Q000494:pharmacology; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D006410:Hematopoiesis / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008817:Mice, Mutant Strains; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010022:Osteopetrosis / Q000473:pathology / Q000503:physiopathology; D011994:Recombinant Proteins / Q000502:physiology
D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D002117:Calcitriol