Reciprocal gene expression of osteoclastogenesis inhibitory factor and osteoclast differentiation factor regulates osteoclast formation.
Osteoblasts/stromal cells support the formation of osteoclast-like cells (OCL) from osteoclast progenitor cells via expressing a membrane-associated protein, osteoclast differentiation factor (ODF), in the presence of osteotropic factors, whereas the cells secrete a substantial amount of osteoclastogenesis inhibitory factor (OCIF) in the unstimulated state. There are both OCL formation-supporting and the nonsupporting cell lines in osteoblasts/stromal cell lineages. The mechanism that divides osteoblasts/stromal cell lines into the two types is not known. The present study reports that OCL formation-supporting cell line ST2 showed a greatly increased level of ODF mRNA, whereas their OCIF mRNA was drastically diminished in the presence of 1alpha, 25(OH)2-dihydroxyvitamin D3 or prostaglandin E2. In contrast, MC3T3-E1 cells lacking OCL formation-supporting ability did not show a decrease in OCIF mRNA in response to the factors, despite a similar increase in ODF mRNA as ST2 cells. However, inactivated MC3T3-E1 cells secreting nothing supported OCL formation in coculture with human promyelocytic cells, HL60. On the contrary, ST2 cells did not support OCL formation from HL60 cells when cocultured in medium conditioned by 1alpha, 25(OH)2 vitamin D3-treated MC3T3-E1. These findings indicate that reciprocal gene expression of ODF and OCIF in osteoblasts/stromal cells is essential for supporting OCL formation.
Nagai
M
M
Department of Biochemistry, Iwate Medical University School of Dentistry, Uchimaru 19-1, Morioka, Iwate, 020-8505, Japan. mnagai@iwate-med.ac.jp
Sato
N
N
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics* / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D018003:Receptors, Calcitonin / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016707:Tissue Fixation
D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018003:Receptors, Calcitonin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D003907:Dexamethasone; D002117:Calcitriol; D015232:Dinoprostone