title: Neonatal changes of osteoclasts in osteopetrosis (op/op) mice defective in production of functional macrophage colony-stimulating factor (M-CSF) protein and effects of M-CSF on osteoclast development and differentiation.
abstract: In mice homozygous for the osteopetrosis (op) mutation, loss of osteoclasts in the postnatal period and their development, differentiation, and maturation following daily M-CSF administration in adult life were investigated. Histochemical, immunohistochemical, and ultrastructural approaches, as well as [3H]thymidine autoradiography, clarified the role of M-CSF on osteoclast development and differentiation. In op/op mice osteoclasts appeared normal at birth. However, osteoclast numbers were reduced within a few days after birth, and osteoclasts were undetectable by 3-4 days of age. In adult op/op mice there were no multinuclear osteoclasts; however, small numbers of mononuclear cells (so-called 'preosteoclasts') were observed on the endosteal surface of bone. These preosteoclasts expressed tartrate-resistant acid phosphatase and showed ultrastructural features of immature osteoclasts. After daily M-CSF administration in op/op mice, osteoclasts developed from the fusion of preosteoclasts and osteoclasts numbers increased to the levels of normal littermates at 3 days. Autoradiographic analysis with [3H]thymidine revealed no labeling in osteoclasts and preosteoclasts. In the mutant mice, M-CSF administration induced numerical increases of monocytes, promonocytes, and earlier precursor cells in bone marrow, ER-MP12- or, ER-MP58-positive granulocyte/macrophage colony-forming cells (GM-CFCs). Among these macrophage precursors, ER-MP58-positive cells were considered preosteoclast precursors, and possessed marked proliferative potential. These data suggest that an ER-MP58-positive cell subpopulation of GM-CFCs proliferates in response to M-CSF, differentiates into preosteoclasts which fuse with each other to develop into mature osteoclasts.
authors.affiliation: Second Department of Pathology, Kumamoto University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Umeda
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Naito
authors.forename: L D
authors.initials: LD
authors.lastname: Shultz
authors.forename: K
authors.initials: K
authors.lastname: Takagi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000848:Anodontia / Q000209:etiology / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D001842:Bone and Bones / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002459:Cell Fusion / Q000187:drug effects; D007180:Incisor; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure; D010010:Osteoclasts / Q000187:drug effects / Q000648:ultrastructure*; D010022:Osteopetrosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D013234:Stem Cells / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D015415:Biomarkers; D016173:Macrophage Colony-Stimulating Factor