Faculty Research 1990 - 1999

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.

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Animals-Newborn, Anodontia: et, pa, Apoptosis: de, Biological-Markers, Bone-and-Bones: pa, Bone-Marrow: de, pa, Cell-Differentiation: de, Cell-Division: de, Cell-Fusion: de, Incisor, Macrophage-Colony-Stimulating-Factor: ge, df, Mice, Mice-Inbred-C3H, Mice-Inbred-C57BL, Mice-Mutant-Strains, Organelles: de, ul, Osteoclasts: de, ul, Osteopetrosis: dt, ge, pa, Stem-Cells: de, ul, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

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J Submicrosc Cytol Pathol 1996 Jan;28(1):13-26




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.

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