Regulation of osteoclastogenesis by three human RANKL isoforms expressed in NIH3T3 cells.
Receptor activator of nuclear factor-kappaB ligand (RANKL) induces osteoclastogenesis by binding with the receptor, receptor activator of nuclear factor-kappaB in the presence of macrophage colony-stimulating factor. Three human RANKL isoforms, hRANKL1, hRANKL2, and hRANKL3, were identified. hRANKL1 was identical to previously reported RANKL and possessed intracellular, transmembrane, and extracellular domains, hRANKL2 did not have the intracellular domain, and hRANKL3 did not have the intracellular and transmembrane domains. When bone marrow macrophages were cultured with NIH3T3 cells expressing hRANKL1, osteoclasts were formed, but when cultured with NIH3T3 cells expressing hRANKL2 or hRANKL3, no tartrate resistant acid phosphatase-positive cell was observed. In the coculture system, coexpression of hRANKL3 with hRANKL1 significantly inhibited the formation of osteoclasts by hRANKL1, but coexpression of hRANKL2 with hRANKL1 did not affect the osteoclastogenesis by hRANKL1 significantly. These results suggest that the activity of osteoclastogenesis by hRANKL1 is regulated by the attenuator, hRANKL3.
Suzuki
Junko
J
Department of Pathology and Immunology, Aging and Developmental Science, Graduate School, Tokyo Medical and Dental University, 113-8519, Tokyo, Japan.
Ikeda
Tohru
T
Kuroyama
Hiroyuki
H
Seki
Sachiko
S
Kasai
Michiyuki
M
Utsuyama
Masanori
M
Tatsumi
Masashi
M
Uematsu
Hiroshi
H
Hirokawa
Katsuiku
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010010:Osteoclasts / Q000166:cytology*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; 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