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.
MeSH terms
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Amino Acid Sequence
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Animals
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Bone Density / physiology*
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Bone Resorption
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Cell Differentiation / drug effects
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Cells, Cultured
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Cricetinae
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Female
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Gene Expression Regulation, Developmental
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Glycoproteins / genetics
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Glycoproteins / metabolism
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Glycoproteins / pharmacology
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Glycoproteins / physiology*
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Humans
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Liver / metabolism
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Male
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Organ Specificity
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Osteoclasts / cytology
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Osteoclasts / drug effects*
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Osteopetrosis / genetics*
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Osteopetrosis / metabolism
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Osteoprotegerin
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Ovariectomy
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RNA, Messenger / analysis
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Rats
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Rats, Inbred F344
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Receptors, Cytoplasmic and Nuclear*
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Receptors, Tumor Necrosis Factor
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Recombinant Fusion Proteins
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Sequence Homology, Amino Acid
Substances
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Glycoproteins
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Osteoprotegerin
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Receptors, Tumor Necrosis Factor
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Recombinant Fusion Proteins
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TNFRSF11B protein, human
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Tnfrsf11b protein, mouse
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Tnfrsf11b protein, rat
Associated data
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GENBANK/U94330
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GENBANK/U94331
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GENBANK/U94332