title: Osteoprotegerin reduces the serum level of receptor activator of NF-kappaB ligand derived from osteoblasts.
abstract: Osteoprotegerin (OPG) is a decoy receptor for receptor activator of NF-kappaB ligand (RANKL). We previously reported that OPG deficiency elevated the circulating level of RANKL in mice. Using OPG(-/-) mice, we investigated whether OPG is involved in the shedding of RANKL by cells expressing RANKL. Osteoblasts and activated T cells in culture released a large amount of RANKL in the absence of OPG. OPG or a soluble form of receptor activator of NF-kappaB (the receptor of RANKL) suppressed the release of RANKL from those cells. OPG- and T cell-double-deficient mice showed an elevated serum RANKL level equivalent to that of OPG(-/-) mice, indicating that circulating RANKL is mainly derived from bone. The serum level of RANKL in OPG(-/-) mice was increased by ovariectomy or administration of 1alpha,25-dihydroxyvitamin D(3). Expression of RANKL mRNA in bone, but not thymus or spleen, was increased in wild-type and OPG(-/-) mice by 1alpha,25-dihydroxyvitamin D(3). These results suggest that OPG suppresses the shedding of RANKL from osteoblasts and that the serum RANKL in OPG(-/-) mice exactly reflects the state of bone resorption.
authors.affiliation: Institute for Oral Science, Matsumoto Dental University, Nagano, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakamichi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Udagawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Midrori
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Teruhito
authors.initials: T
authors.lastname: Yamashita
authors.forename: Toshihide
authors.initials: T
authors.lastname: Mizoguchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sato
authors.forename: Makio
authors.initials: M
authors.lastname: Mogi
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takahashi
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism; D002117:Calcitriol / Q000008:administration & dosage; D008024:Ligands; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000201:enzymology / Q000378:metabolism*; D053244:Osteoprotegerin / Q000235:genetics / Q000502:physiology*; D053245:RANK Ligand / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism
chemical_list: D008024:Ligands; D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C505689:Tnfsf11 protein, mouse; D051722:ADAM Proteins; D053504:Matrix Metalloproteinases, Membrane-Associated; D000072198:ADAM17 Protein; D002117:Calcitriol