Novel Aspects on RANK Ligand and Osteoprotegerin in Osteoporosis and Vascular Disease

Sattler, Alexander M.; Schoppet, Michael; Schaefer, Jürgen R.; Hofbauer, Lorenz C.

doi:10.1007/s00223-003-0011-y

Cited by 107 publications

(96 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The strong positive relation we found between age and OPG was previously described in men (17,26,27), elderly women (15,23), and diabetic subjects (27) and has been interpreted as a compensatory mechanism counteracting the age progression of bone resorption and atherosclerosis (16,17,19,28). This increase was also linked to the expected modifications in renal function observed with age.…”

Section: Discussionsupporting

confidence: 81%

Osteoprotegerin in relation to body weight, lipid parameters insulin sensitivity, adipocytokines, and C-reactive protein in obese and non-obese young individuals: results from both cross-sectional and interventional study

Gannagé‐Yared¹,

Yaghi²,

Habre³

et al. 2008

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: We analyzed the relation of osteoprotegerin (OPG) with insulin sensitivity, lipid profile, serum glutamic pyruvic transaminase (SGPT), adipocytokines, and C-reactive protein (CRP) in obese and non-obese subjects. Methods: In the study, 170 subjects (106 obese and 64 non-obese, sex ratio female/maleZ2.03) were included. Thirty-two obese subjects were reevaluated 6 months after the weight loss induced by bariatric surgery. Results: OPG did not differ between obese and non-obese subjects (respective mean values 5.17 and 4.96 pmol/l) or according to gender, but was positively correlated with age (P!0.0001 for both groups). OPG was statistically higher in 18 obese diabetic subjects compared with non-diabetics (PZ0.03). After adjustment for age, no significant correlation was found between OPG and body mass index (BMI), waist, systolic and diastolic blood pressure, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, leptin, and adiponectin in both the obese and non-obese subjects. However, OPG was positively correlated with homeostasis model assessment (HOMA) index and SGPT levels in obese subjects at baseline (rZ0.295, rZ0.20, P!0.05) and after adjustment for age (rZ 0.28, rZ0.20, P!0.05). OPG was also significantly correlated with CRP; this correlation persisted after adjustment for age in obese subjects (rZ0.30, P!0.01). In a multivariate analysis in the obese group, HOMA index and CRP were independent predictors of OPG while SGPT was not. Six months post-surgery, OPG did not change, despite a significant reduction in glucose, SGPT, cholesterol, triglycerides, CRP, and leptin values (PZ0.02, PZ0.006, PZ0.007, P!0.001, P!0.001, P!0.001 respectively) and a significant increase in adiponectin and HDL values (P!0.001 for both variables). Conclusion: Our results show that in obese subjects, OPG is not related to BMI. However, we describe new relationships between OPG and both HOMA index and CRP.

show abstract

Section: Discussionsupporting

confidence: 81%

Osteoprotegerin in relation to body weight, lipid parameters insulin sensitivity, adipocytokines, and C-reactive protein in obese and non-obese young individuals: results from both cross-sectional and interventional study

Gannagé‐Yared¹,

Yaghi²,

Habre³

et al. 2008

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…In general, serum RANKL levels appear unaltered, although they have sometimes declined as serum OPG levels increased. 20,21,43 Furthermore, in a recent study, Kiechl et al showed in a large scale epidemiological study that serum RANKL levels did not correlate with atherosclerosis, but baseline RANKL levels were shown to be a predictor of vascular risk. 44 Thus, the role of serum RANKL levels as predictors of cardiovascular risk is unclear.…”

Section: Discussionmentioning

confidence: 99%

RANKL Increases Vascular Smooth Muscle Cell Calcification Through a RANK-BMP4–Dependent Pathway

Panizo¹,

Cardús²,

Encinas³

et al. 2009

Circulation Research

220

157

View full text Add to dashboard Cite

Abstract-Vascular calcification commonly associated with several pathologies and it has been suggested to be similar to bone mineralization. The axis RANKL-OPG (receptor activator of nuclear factor B ligand-osteoprotegerin) finely controls bone turnover. RANKL has been suggested to increase vascular calcification, but direct evidence is missing. Thus, in the present work, we assess the effect of RANKL in vascular smooth muscle cell (VSMC) calcification. VSMCs incubated with RANKL showed a dose-dependent increase in calcification, which was abolished by coincubation with OPG. To test whether the effect was mediated by signaling to its receptor, knockdown of RANK was accomplished by short hairpin (sh)RNA. Indeed, cells lacking RANK showed no increases in vascular calcification when incubated with RANKL. To further elucidate the mechanism by which RANK activation increases calcification, we blocked both nuclear factor (NF)-B activation pathways. Only IKK␣ inactivation inhibited calcification, pointing to an involvement of the alternative NF-B activation pathway. Furthermore, RANKL addition increased bone morphogenetic protein (BMP)4 expression in VSMCs, and that increase disappeared in cells lacking RANK or IKK␣. The increase in calcification was also blunted by Noggin, pointing to a mediation of BMP4 in the calcification induced by RANKL. Furthermore, in an in vivo model, the increase in vascular calcium content was parallel to an increase in RANKL and BMP4 expression, which was localized in calcified areas. However, blood levels of the ratio RANKL/OPG did not change. We conclude that RANKL increases vascular smooth muscle cell calcification by binding to RANK and increasing BMP4 production through activation of the alternative NF-B pathway.

show abstract

“…The clinical coincidence of osteoporosis and vascular disease has long indicated that common mediators may adversely affect both bone metabolism and vascular integrity (14). Osteoprotegerin binds to RANKL and tumor necrosis factor-related apoptosis-inducing ligand (15), thereby inhibiting the ligation of these mediators to their receptors and inhibiting their subsequent activation of specific proinflammatory and proapoptotic signaling pathways (16).…”

Section: Discussionmentioning

confidence: 99%

The Relationship Between Plasma Osteoprotegerin and Endothelium-Dependent Arterial Dilation in Type 2 Diabetes

Gao

Zhao

et al. 2006

Diabetes

View full text Add to dashboard Cite

Osteoprotegerin is a recently identified inhibitor of bone resorption. Recent studies indicate that osteoprotegerin also acts as an important regulatory molecule in the vasculature. The purpose of this study was to investigate the relationship between plasma osteoprotegerin levels and endothelium-dependent arterial dilation in type 2 diabetic patients. The study subjects included 40 newly diagnosed type 2 diabetic patients and 46 healthy subjects. All patients were given insulin therapy for 6 months. Plasma osteoprotegerin concentration was measured in duplicate by a sandwich enzyme-linked immunosorbent assay method, and high-resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual glyceryltrinitrate. The plasma osteoprotegerin level in patients before treatment was 3.36 ؎ 0.32 ng/l, which was significantly higher than that in control subjects (2.38 ؎ 0.25 ng/l, P < 0.001). After 6 months of treatment, osteoprotegerin levels decreased markedly (2.83 ؎ 0.34 ng/l, P < 0.001). Flow-mediated endothelium-dependent arterial dilation in patients before treatment was 3.21 ؎ 0.52%, which was significantly lower than that in control subjects (4.46 ؎ 0.56%, P < 0.01), and it improved markedly after 6 months of treatment (4.03 ؎ 0.49%, P < 0.01). In multivariate analysis, osteoprotegerin was significantly associated with endothelium-dependent arterial dilation, fasting blood glucose (FBG), HbA 1c (A1C), and ultrasensitive C-reactive protein (CRP) at baseline (P < 0.01). The absolute changes in osteoprotegerin showed significant correlation with changes in endothelium-dependent arterial dilation, FBG, A1C, and CRP in diabetic patients during the course of treatment (P < 0.01). This study shows that plasma osteoprotegerin levels are elevated in newly diagnosed diabetic patients and are significantly associated with endothelial function. Diabetes 55:2126 -2131, 2006 O steoprotegerin, a recently identified glycoprotein belonging to the tumor necrosis factor receptor superfamily, was originally discovered as an inhibitor of bone resorption. This inhibition is mediated through osteoprotegerin's binding and neutralization of the receptor activator of nuclear factor-B ligand (RANKL), a strong inducer of osteoclast differentiation (1). Recently, some studies have indicated that osteoprotegerin also acts as an important regulatory molecule in the vasculature (2-6), and increased plasma osteoprotegerin concentrations are associated with coronary artery disease in nondiabetic patients (6,7). In some more recent studies in diabetic subjects, a strong association between plasma levels of osteoprotegerin and microand macroangiopathy was observed (8,9). Moreover, in a large observational study, plasma concentrations of osteoprotegerin were higher in diabetic than in nondiabetic subjects (10). Endothelial dysfunction is an early physiological event in atherosclerosis (11). However, to date, no data are available on the relationship between osteoprotegerin and endothelial dysf...

show abstract

Novel Aspects on RANK Ligand and Osteoprotegerin in Osteoporosis and Vascular Disease

Cited by 107 publications

References 24 publications

Osteoprotegerin in relation to body weight, lipid parameters insulin sensitivity, adipocytokines, and C-reactive protein in obese and non-obese young individuals: results from both cross-sectional and interventional study

Osteoprotegerin in relation to body weight, lipid parameters insulin sensitivity, adipocytokines, and C-reactive protein in obese and non-obese young individuals: results from both cross-sectional and interventional study

RANKL Increases Vascular Smooth Muscle Cell Calcification Through a RANK-BMP4–Dependent Pathway

The Relationship Between Plasma Osteoprotegerin and Endothelium-Dependent Arterial Dilation in Type 2 Diabetes

Contact Info

Product

Resources

About