Simonet et al. (1997) identified a secreted glycoprotein that regulates bone resorption. The human protein, termed
osteoprotegerin (OPG), is a member of the tumor necrosis factor (TNF) receptor superfamily and contains 401 amino
acids. 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.
They concluded that OPG can act as a soluble factor in the regulation of bone mass and speculated that
OPG may be useful in the treatment of osteoporosis associated with increased osteoclast activity.
NCBI Summary:
The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein is an osteoblast-secreted decoy receptor that functions as a negative regulator of bone resorption. This protein specifically binds to its ligand, osteoprotegerin ligand, both of which are key extracellular regulators of osteoclast development. Studies of the mouse counterpart also suggest that this protein and its ligand play a role in lymph-node organogenesis and vascular calcification. Alternatively spliced transcript variants of this gene have been reported, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]
General function
Receptor
Comment
Cellular localization
Secreted
Comment
Circulating osteoprotegerin and soluble receptor activator of nuclear factor κB ligand in polycystic ovary syndrome: relationships to insulin resistance and endothelial dysfunction. Pepene CE et al. (2010) There is plenty of evidence that osteoprotegerin (OPG) is linked to subclinical vascular damage and predicts cardiovascular disease in high-risk populations. Our aim is to investigate the relationships of OPG/free soluble receptor activator of nuclear factor κB ligand (sRANKL) to insulin resistance, brachial artery flow-mediated vasodilation (FMD), and the carotid artery intima-media thickness (CIMT) in polycystic ovary syndrome (PCOS), a disorder characterized by hyperandrogenism, impaired glucose control, and endothelial injury. A cross-sectional, observational study. Hormonal and metabolic profiles, FMD, CIMT, serum OPG, and ampli-sRANKL were assessed in 64 young PCOS patients and 20 controls of similar age. Body composition was measured by dual energy X-ray absorptiometry. OPG was significantly lower in PCOS and related negatively to free testosterone and positively to estradiol (E(2)) levels. In multivariate analysis, OPG but not ampli-sRANKL correlated positively to fasting insulin, insulin sensitivity indices, and FMD. Neither OPG nor ampli-sRANKL was associated with CIMT. Significantly lower adjusted FMD values were demonstrated in women in the upper OPG quartile group (>2.65 pmol/l) compared with all other quartile groups together (P=0.012). In PCOS, multiple regression analysis retained E(2)/sex hormone-binding globulin ratio, fat mass, and homeostasis model assessment of insulin resistance as independent predictors of OPG. In PCOS, circulating OPG is related to both endothelial dysfunction and insulin resistance, independent of obesity and androgen excess, suggesting OPG as a useful biomarker of these effects. Further studies are needed to evaluate OPG in relation to cardiovascular events and cardiovascular mortality in PCOS.//////////////////
Ovarian function
Comment
Circulating osteoprotegerin and soluble receptor activator of NFKB ligand in polycystic ovary syndrome: relationships to insulin resistance and endothelial dysfunction. Pepene CE et al. Objective: There is plenty of evidence that osteoprotegerin (OPG) is linked to subclinical vascular damage and predicts cardiovascular disease in high-risk populations. Our aim was to investigate the relationships of OPG/free soluble receptor activator of nuclear factor kappa B ligand (sRANKL) to insulin resistance, brachial artery flow-mediated vasodilatation (FMD) and the carotid artery intima-media thickness (CIMT) in polycystic ovary syndrome (PCOS), a disorder characterized by hyperandrogenism, impaired glucose control and endothelial injury. Design: Cross-sectional, observational study. Methods: Hormonal and metabolic profiles, FMD, CIMT, serum OPG and ampli-sRANKL were assessed in 64 young PCOS patients and 20 controls of similar age. Body composition was measured by dual energy X-ray absorptiometry. Results: OPG was significantly lower in PCOS and related negatively to free testosterone (FT) and positively to estradiol (E(2)) levels. In multivariate analysis, OPG but not ampli-sRANKL correlated positively to fasting insulin, insulin sensitivity indices and FMD. Neither OPG nor ampli-sRANKL was associated with CIMT. Significantly lower adjusted FMD values were demonstrated in women in the upper OPG quartile group (>2.65 pmol/l) compared to all other quartile groups together (p = 0.012). In PCOS, multiple regression analysis retained E(2)/SHBG ratio, fat mass and HOMA-IR as independent predictors of OPG. Conclusions: In PCOS, circulating OPG is related to both endothelial dysfunction and insulin resistance, independently of obesity and androgen excess, suggesting OPG as a useful biomarker of these effects. Further studies are needed to evaluate OPG in relation to cardiovascular events and cardiovascular mortality in PCOS.
Expression regulated by
Steroids
Comment
Ovarian localization
Granulosa
Comment
Robert A Mastroeni, Deborah M Sindoni, Dana M Banas, Georgius
de Haan, Donald E Frail, Susan L Fitzpatrick reported the identification and Characterization of Osteopontin and
Other Estrogen Regulated Genes in Rat and Mouse Granulosa
Cells In Vivo.
By the use of Rapid Analysis of Differential Expression, a
type of differential display, genes that were regulated by
17b-estradiol (E2) in vivo (1.5 mg daily for 3 days) were
identified in granulosa cells from immature rats. Fucosidase mRNA
expression was up regulated approximately 5-fold whereas
osteopontin (OPN), osteoprotegerin, and aldehyde dehydrogenase
mRNAs were down regulated approximately 5-fold. These results
were confirmed by Northern blot analysis and/or quantitative
RT-PCR.
Follicle stages
Antral
Comment
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment:Bucay et al. (1998) investigated the physiologic role of OPG by generating OPG-deficient mice. Adolescent and adult
mice with the disrupted gene, OPG -/-, exhibited a decrease in total bone density characterized by severe trabecular and
cortical bone porosity, marked thinning of the parietal bones of the skull, and a high incidence of fractures. These
findings demonstrated that OPG is a critical regulator of postnatal bone mass. Unexpectedly, OPG-deficient mice also
exhibited medial calcification of the aorta and renal arteries, suggesting that regulation of OPG, its signaling pathway,
or its ligand(s) may play a role in the long observed association between osteoporosis and vascular calcification.