Macrophage colony-stimulating factor increases bone resorption by osteoclasts disaggregated from human fetal long bones.
Macrophage colony-stimulating factor (M-CSF) is known to play an important role in human and murine osteoclast formation. Although M-CSF has been shown to inhibit isolated neonatal rat osteoclasts from resorbing bone, its action on the mature human osteoclast has not been described. We now report that M-CSF increases osteoclastic bone resorption in a dose-responsive manner. Bone resorption by mature human fetal osteoclasts, including pit area, depth, and volume, was increased in the presence of M-CSF compared with vehicle. The number of osteoclasts in the cultures was similar after 2 and 18 h in the presence of M-CSF, whereas there was a significant reduction in osteoclast number, whether assessed as the number of tartrate-resistant acid phosphatase (TRAP)-positive or vitronectin receptor-positive cells after 18 h in M-CSF-free cultures. The number of nuclei per osteoclast after 2 or 18 h in M-CSF was also similar and there was no difference in the number of vitronectin receptor-positive mononucleate cells at 2 and 18 h. This suggests that the increased bone resorption is likely to be accounted for by enhanced osteoclast survival in M-CSF compared with controls rather than by formation of new osteoclasts.
Edwards
M
M
Department of Histopathology, Imperial College School of Medicine at St. Mary's, London, UK.
Sarma
U
U
Flanagan
A M
AM
D000135:Acid Phosphatase / Q000032:analysis; D001862:Bone Resorption / Q000139:chemically induced / Q000196:embryology / Q000209:etiology*; D001842:Bone and Bones / Q000187:drug effects / Q000196:embryology; D002452:Cell Count; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D016173:Macrophage Colony-Stimulating Factor / Q000633:toxicity*; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000032:analysis; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors
D007527:Isoenzymes; D019030:Receptors, Vitronectin; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase