title: Roles of macrophage-colony stimulating factor and osteoclast differentiation factor in osteoclastogenesis.
abstract: We have isolated osteoclast precursors (OCPs) from cocultures of mouse calvarial cells and bone marrow cells without adding any osteotropic factors. OCPs expressed Mac-1, Mac-2, and Gr-1 antigens but not osteoclast markers such as tartrate-resistant acid phosphatase (TRAP) and calcitonin receptors, and they differentiated into TRAP-positive cells within 48 h on a fixed calvarial cell layer pretreated with osteotropic factors such as 1 alpha, 25-dihydroxyvitamin D3. In the present study, we investigated the regulatory mechanisms of OCP formation from hemopoietic cells and TRAP-positive cell formation from OCPs. Calvarial osteoblasts obtained from macrophage-colony stimulating factor (M-CSF)-deficient op/op mice failed to support OCP formation or the differentiation of OCPs into TRAP-positive cells. Both OCP formation and TRAP-positive cell formation supported by osteoblasts were completely inhibited by osteoclastogenesis inhibitory factor (OCIF, also called OPG), which is a decoy receptor of osteoclast differentiation factor (ODF; also called TRANCE, RANKL, and OPGL). When bone marrow cells were cultured for 4 days with soluble ODF (sODF/sRANKL) together with M-CSF, OCPs were formed even in the absence of osteoblasts. When OCPs were treated with sODF/sRANKL and M-CSF in the absence of osteoblasts, they differentiated into TRAP-positive cells within 48 h even in the presence of hydroxyurea. Northern blotting analysis revealed that osteoblasts constitutively expressed a certain level of ODF/RANKL mRNA. These results indicated that M-CSF and sODF/sRANKL produced by osteoblasts are two essential factors for both OCP formation and TRAP-positive osteoclast formation.
authors.affiliation: Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tsurukai
authors.forename: N
authors.initials: N
authors.lastname: Udagawa
authors.forename: K
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Suda
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D000831:Animals, Newborn; D002117:Calcitriol / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007527:Isoenzymes / Q000032:analysis; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000378:metabolism; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D002117:Calcitriol; D006918:Hydroxyurea