title: Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
abstract: A novel secreted glycoprotein that regulates bone resorption has been identified. The protein, termed Osteoprotegerin (OPG), is a novel member of the TNF receptor superfamily. In vivo, hepatic expression of OPG in transgenic mice results in a profound yet nonlethal osteopetrosis, coincident with a decrease in later stages of osteoclast differentiation. These same effects are observed upon administration of recombinant OPG into normal mice. In vitro, osteoclast differentiation from precursor cells is blocked in a dose-dependent manner by recombinant OPG. Furthermore, OPG blocks ovariectomy-associated bone loss in rats. These data show that OPG can act as a soluble factor in the regulation of bone mass and imply a utility for OPG in the treatment of osteoporosis associated with increased osteoclast activity.
authors.affiliation: Department of Molecular Genetics, Amgen Inc., Thousand Oaks, California 91320, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Simonet
authors.forename: D L
authors.initials: DL
authors.lastname: Lacey
authors.forename: C R
authors.initials: CR
authors.lastname: Dunstan
authors.forename: M
authors.initials: M
authors.lastname: Kelley
authors.forename: M S
authors.initials: MS
authors.lastname: Chang
authors.forename: R
authors.initials: R
authors.lastname: Lüthy
authors.forename: H Q
authors.initials: HQ
authors.lastname: Nguyen
authors.forename: S
authors.initials: S
authors.lastname: Wooden
authors.forename: L
authors.initials: L
authors.lastname: Bennett
authors.forename: T
authors.initials: T
authors.lastname: Boone
authors.forename: G
authors.initials: G
authors.lastname: Shimamoto
authors.forename: M
authors.initials: M
authors.lastname: DeRose
authors.forename: R
authors.initials: R
authors.lastname: Elliott
authors.forename: A
authors.initials: A
authors.lastname: Colombero
authors.forename: H L
authors.initials: HL
authors.lastname: Tan
authors.forename: G
authors.initials: G
authors.lastname: Trail
authors.forename: J
authors.initials: J
authors.lastname: Sullivan
authors.forename: E
authors.initials: E
authors.lastname: Davy
authors.forename: N
authors.initials: N
authors.lastname: Bucay
authors.forename: L
authors.initials: L
authors.lastname: Renshaw-Gegg
authors.forename: T M
authors.initials: TM
authors.lastname: Hughes
authors.forename: D
authors.initials: D
authors.lastname: Hill
authors.forename: W
authors.initials: W
authors.lastname: Pattison
authors.forename: P
authors.initials: P
authors.lastname: Campbell
authors.forename: S
authors.initials: S
authors.lastname: Sander
authors.forename: G
authors.initials: G
authors.lastname: Van
authors.forename: J
authors.initials: J
authors.lastname: Tarpley
authors.forename: P
authors.initials: P
authors.lastname: Derby
authors.forename: R
authors.initials: R
authors.lastname: Lee
authors.forename: W J
authors.initials: WJ
authors.lastname: Boyle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015519:Bone Density / Q000502:physiology*; D001862:Bone Resorption; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D010022:Osteopetrosis / Q000235:genetics* / Q000378:metabolism; D053244:Osteoprotegerin; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid
chemical_list: D006023:Glycoproteins; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse; C506032:Tnfrsf11b protein, rat