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Role of RANKL-RANK/osteoprotegerin pathway in cardiovascular and bone disease associated with HIV infection.

ABSTRACT: Patients with HIV?1 infection often develop multiple complications and comorbidities, including osteoporosis and atherosclerosis. The receptor activator of nuclear factor kappa-B/receptor activator of nuclear factor kappa-B ligand/osteoprotegerin axis has been identified as a possible common link between osteoporosis and vascular diseases. Since the discovery of this axis, much has been learned about its role in controlling skeletal biology and less about its role in the context of vascular biology. However, the exact role of the receptor activator of nuclear factor kappa-B ligand/osteoprotegerin axis in HIV infection is not completely understood. In this review we examine the mechanisms by which inflammation and immune dysregulation in HIV?1 infection may impact bone turnover and atherogenesis through perturbations in the receptor activator of nuclear factor kappa-B/receptor activator of nuclear factor kappa-B ligand/osteoprotegerin axis.

SUBMITTER: Kelesidis T

PROVIDER: S-EPMC5067015 | biostudies-literature | 2014 Jul-Sep

REPOSITORIES: biostudies-literature

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Role of RANKL-RANK/osteoprotegerin pathway in cardiovascular and bone disease associated with HIV infection.

Kelesidis Theodoros T Currier Judith S JS Yang Otto O OO Brown Todd T TT

AIDS reviews 20140701 3

Patients with HIV‑1 infection often develop multiple complications and comorbidities, including osteoporosis and atherosclerosis. The receptor activator of nuclear factor kappa-B/receptor activator of nuclear factor kappa-B ligand/osteoprotegerin axis has been identified as a possible common link between osteoporosis and vascular diseases. Since the discovery of this axis, much has been learned about its role in controlling skeletal biology and less about its role in the context of vascular biol ...[more]

PMID: 25102334

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Project description:We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r (2) ? 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40-79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm(3)) and cross-sectional area (mm(2)) at the 4% site and cortical vBMD (mg/mm(3)); total, cortical, and medullary area (mm(2)); cortical thickness (mm); and stress strain index (SSI) (mm(3)) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (? [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (? [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (? [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (? [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (? [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (? [95% CI] = -0.08 [-0.13 to -0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (? [95% CI] = -7.58 [-14.01 to -1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (? [95% CI] = 8.90 [0.92-16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men.

Dataset Information

Role of RANKL-RANK/osteoprotegerin pathway in cardiovascular and bone disease associated with HIV infection.

Publications

Role of RANKL-RANK/osteoprotegerin pathway in cardiovascular and bone disease associated with HIV infection.

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