Association between osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL levels, and bone mineral density in Korean postmenopausal women

Kim, Jung Gu; Kim, Jung Hwa; Kim, Ja Yeon; Ku, Seung Yup; Jee, Byung Chul; Suh, Chang Suk; Kim, Seok Hyun; Choi, Young Min

doi:10.1097/gme.0b013e31802d976f

Cited by 98 publications

(85 citation statements)

References 22 publications

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“…(36) Previous candidate gene association studies also have reported an association between rs2073618 and LS BMD a . (15,25,26,29) This association has been confirmed in a meta-analysis study by Lee and colleagues as well. (44) In our study, the minor alleles of rs2073618 and rs9594738 were associated with lower LS BMD a .…”

Section: Discussionmentioning

confidence: 53%

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Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men

Roshandel

Holliday

Pye

et al. 2010

Journal of Bone and Mineral Research

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The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r 2 ! 0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMD a ) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP rs9594759 (C) was associated with lower PINP (b ¼ À1.84, p ¼ .003) and CTX-I (b ¼ À27.02, p ¼ 6.06 Â 10 À8 ) and higher ultrasound BMD at the calcaneus (b ¼ 0.01, p ¼ .037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men. ß

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Section: Discussionmentioning

confidence: 53%

“…(27) In contrast, other studies did not find any significant association between rs2073618 and bone turnover markers, but these studies were relatively small. (15,19,28) The other five SNPs have not been tested previously in association with bone turnover markers.…”

Section: Discussionmentioning

confidence: 99%

Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men

Roshandel

Holliday

Pye

et al. 2010

Journal of Bone and Mineral Research

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“…We found an association between the rs3102735 polymorphism and BMD, but did not find any effect on the fracture risk; however, the present study was underpowered to show small effects. Other authors (16,17,35) have reported no effect of this genetic variation on BMD. There are several possible explanations for these discrepancies.…”

Section: Discussionmentioning

confidence: 99%

“…Polymorphisms of the TNFRSF11B gene may contribute to the genetic regulation of bone mass as suggested by several recent publications, but the results are somewhat contradictory (12)(13)(14)(15)(16). The ambiguous results include the frequently investigated rs3102735 single nucleotide polymorphism (SNP) effects on BMD and fracture risk (14,17). Recently, an association between BMD and SNPs of OPG gene has been demonstrated during a genome-wide screening (18,19).…”

Section: Introductionmentioning

confidence: 99%

Allelic variations of RANKL/OPG signaling system are related to bone mineral density and in vivo gene expression

Takács

Lazáry

Kósa

et al. 2010

European Journal of Endocrinology

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Objective: Receptor activator of nuclear factor-kB ligand/osteoprotegerin (RANKL/OPG) signaling system plays a crucial role in the regulation of bone resorption. Polymorphic variations in the genes may have an influence on gene expression and bone metabolism. In the present study, we aimed to investigate the influence of RANKL/OPG allelic variations on the in vivo human gene expression of five genes, bone mineral density (BMD), and fracture incidence in Hungarian postmenopausal women. Methods: Three hundred and sixty postmenopausal women (61.6G7.9 years) were genotyped. All together, five single nucleotide polymorphisms (SNPs) in the two genes have been investigated. In addition, bone samples from 17 examined subjects were acquired for gene expression studies. Bone densities and fracture data have also been collected. Results: All two SNPs in OPG gene and three SNPs in RANKL gene showed correlation with BMD. Haplotype analysis of these genes gave similar results. The 'CCT' haplotype of RANKL promoter region, which was associated with decreased BMD, exhibited a significantly upregulated expression of RANKL mRNA, while the other haplotypes of RANKL or OPG 15 genes did not. No correlation between genetic variations and fracture data was found. Conclusion: We have demonstrated associations between RANKL and OPG haplotypes and BMD as well as between RANKL haplotypes and in vivo RANKL expression in a Hungarian postmenopausal population. Moreover, we have found a new RANKL haplotype associating with reduced BMD and increased in vivo RANKL expression in human bone tissue.

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“…OPG cytokine by binding to RANKL prevents from RANKL binding to RANK receptor on osteoclast cells and inhibits from bone resorption and reduce the process of osteoclastogenesis [32].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Dietary Supplements of Calcium, Vitamin D and Estrogen Hormone on Serum Levels of OPG and RANKL Cytokines and their Relationship with Increased Bone Density in Rats

Piri

Khosravi

Moayeri

et al. 2016

JCDR

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IntRoductIonBone is considered to be one of the hardest living tissues which has an extensive blood supply and is constantly undergoing change [1]. Osteoblasts account for the organic components of bone matrix. Bone surface growth is promoted by deposition of calcium salts in a newly formed matrix [2]. Alkaline phosphatase secreting Osteoblasts, generate matrix vesicles in which crystals of hydroxyapatite (calcium and phosphate deposits) are shaped [3].Osteoclasts secrete collagenase and other enzymes into the subcellular space to make a local acidic environment which dissolves hydroxyapatite and accelerates localized absorption of collagen. Therefore, both cells (osteoblasts, osteoclasts) are coordinated and essential for bone remodeling [4].The bone remodeling process happens with a rate of close to a 100% in the first year of life and 10% in the adult population [5]. The most important micronutrients in maintaining bone health which contribute most to bone mineral density at all ages are calcium, phosphorus, vitamin D [6]. Other studies showed that taking supplements such as calcium and vitamin D promotes bone absorption and resorption [7]. Studies on laboratory animals have also shown that calcium deficiency leads to inhibition of bone formation [8]. Vicky Tai et al., studied the special effects of a diet rich in calcium on bone metabolism in rats. Results indicated that Bone Mineral Density (BMD) of the femur in groups which had consumed calcium rich nutrients were notably higher than that of the control group [9]. During the process of bone formation, fluctuations in estrogen affect bone formation [10].Receptor activator of nuclear factor kappa-B ligand (RANKL), a member of the Tumour Necrosis Factor (TNF) superfamily, is an effective stimulator of both, osteoclast formation and their boneresorbing activity [11]. Upon binding to its receptor, RANK located on osteoclasts, RANKL signaling increases differentiation and activation of the osteoclasts resulting in expression of osteoclast specific molecules. During normal bone remodeling, marrow stromal cells and osteoblasts produce RANKL, which binds to the transmembrane receptor RANK on osteoclast precursors and induces differentiation and activation [12]. This occurs through the transcription factor, nuclear-factor kappa B(NFkB), which is responsible not only for activating osteoclastogenesis but also the body's inflammatory response. Although it has been proposed for a long time that the main source of RANKL are stromal and osteoblastic cells, a very recent study examiners proved that the main RANKL production site resides within osteocytes [13].Osteoprotegerin (OPG) is a secreted by TNF receptor super family member acting as a decoy receptor molecule for RANKL, thereby counteracting its osteoclastogenic activity. It is produced by a variety of cells, including stromal cells, B lymphocytes and dendritic cells [14].Estrogen, the major hormone regulating bone remodeling, is essential for both men and women. Estrogen's role in maintaining bone health is far rea...

show abstract

Association between osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL levels, and bone mineral density in Korean postmenopausal women

Cited by 98 publications

References 22 publications

Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men

Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men

Allelic variations of RANKL/OPG signaling system are related to bone mineral density and in vivo gene expression

The Effects of Dietary Supplements of Calcium, Vitamin D and Estrogen Hormone on Serum Levels of OPG and RANKL Cytokines and their Relationship with Increased Bone Density in Rats

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