title: A RANKL-inducible gene Znf216 in osteoclast differentiation.
abstract: Osteoclasts possess catabolic activity in mineralized tissues and are involved in bone remodeling coordinating with osteoblasts. Although the pathway using receptor and activator of NF-kappa B (RANK) and its ligand, RANKL, is known to be essential for osteoclast differentiation, their precise mechanisms are not fully understood. Using DNA microarray technology, we searched for genes that were up-regulated after RANKL stimulation in the macrophage cell line, RAW264.7 cells. A gene, Znf216, which encodes a zinc-finger protein, was detected among those genes up-regulated after RANKL stimulation. Expression of Znf216 was also induced by other cytokines such as TNFalpha and IL-1beta. Although ectopic expression of full-length ZNF216 abrogated osteoclast differentiation, its truncated forms accelerated it. No significant inhibitory effect on the NF-kappa B pathway was observed, however. These results suggest that ZNF216 is a potent inhibitory factor for osteoclast differentiation and that the mechanism is unlikely due to direct attenuation of the NF-kappa B pathway.
authors.affiliation: Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hishiya
authors.forename: Kyoji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Ken
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D015151:Immunoblotting; D007375:Interleukin-1 / Q000378:metabolism; D008024:Ligands; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D053245:RANK Ligand; D012313:RNA / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D016335:Zinc Fingers; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D007375:Interleukin-1; D008024:Ligands; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011506:Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C114488:ZFAND5 protein, human; D012313:RNA; D004247:DNA; D048051:p38 Mitogen-Activated Protein Kinases