The −9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPα and FOXA1 binding is associated with osteoporosis

Huang, Qihua; Li, Gloria Hoi-Yee; Kung, Annie W. C.

doi:10.1016/j.bone.2009.03.676

Cited by 51 publications

(31 citation statements)

References 38 publications

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“…In vitro, SOST inhibits osteoblast development and stimulates osteoblast apoptosis, resulting in the inhibition of bone formation [18]. In this study, the SOST -9247T>C polymorphism was not related with BMD in postmenopausal Korean women, and this result is contradictory with the results of Huang et al [23] showing an association with BMD at the lumbar spine in a Chinese population. This discrepancy may be due to the difference in study participants and the method of statistical analysis.…”

Section: Discussioncontrasting

confidence: 57%

“…As shown in table 1, 18 single nucleotide polymorphisms (SNPs) in Wnt antagonist genes were selected based on previous reports and the SNP database registered by the National Center for Biotechnology Information (dbSNP), which were composed of non-synonymous SNPs or disease-associated SNPs [23,26,27,28,31]. …”

Section: Methodsmentioning

confidence: 99%

“…To date, several studies have investigated the relationship between bone mass and polymorphisms in these Wnt antagonist genes such as SOST, DKK1, sFRP1, sFRP3 and sFRP4 [21,22,23,24,25,26,27,28,29]. However, the results of these studies were controversial, depending on ethnicity and the type of polymorphisms or studied genes.…”

Section: Introductionmentioning

confidence: 99%

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Association between Polymorphisms in Sclerostin, Dickkopfs and Secreted Frizzled-Related Protein Genes and Bone Mineral Density in Postmenopausal Korean Women

Lee

Kim²,

Ku³

et al. 2014

Gynecol Obstet Invest

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Background/Aims: The purpose of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in sclerostin (SOST), dickkopf (DKK), secreted frizzled-related protein (sFRP) genes and bone mineral density (BMD) in postmenopausal Korean women. Methods: The SOST, Wnt inhibitory factor 1 (WIF1), sFRP1,sFRP2,sFRP3, sFRP4, sFRP5, DKK1, DKK2 and DKK3 polymorphisms were analyzed in 399 postmenopausal Korean women. Serum levels of bone turnover markers were measured, and BMDs at the lumbar spine and femoral neck were also examined. Results: No significant differences in adjusted BMD at the lumbar spine and femoral neck were noted according to any single and combined polymorphisms measured in SOST, DKKs and sFRPs. However, osteoporosis at the femoral neck was 2.35 times more frequently observed in the AA genotype of the sFRP4 c.958C>A polymorphism compared to the non-AA genotype (95% CI 1.09-5.08, p = 0.03). Also, the CC genotype of the sFRP3 c.970C>G polymorphism had a higher rate of osteoporosis at the femoral neck compared to the GC genotype (OR 8.47, 95% CI 1.37-52.63, p = 0.049). Conclusions: Our results suggest that the sFRP3 c.970C>G and sFRP4 c.958C>A polymorphisms may be genetic factors associated with the prevalence of osteoporosis at the femoral neck in postmenopausal Korean women.

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Section: Discussioncontrasting

confidence: 57%

Section: Methodsmentioning

confidence: 99%

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Association between Polymorphisms in Sclerostin, Dickkopfs and Secreted Frizzled-Related Protein Genes and Bone Mineral Density in Postmenopausal Korean Women

Lee

Kim²,

Ku³

et al. 2014

Gynecol Obstet Invest

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“…Given that single-nucleotide polymorphisms of SOST that predispose to increased fracture risk and low BMD have been identified recently, (37)(38)(39)(40) the possibility that PTH may be less effective in these populations demands that additional treatment options are made available.…”

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confidence: 99%

Building bone with a SOST-PTH partnership

Sims

2010

Journal of Bone and Mineral Research

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T he discovery of the SOST gene, whose protein product, sclerostin, is an osteocyte-derived inhibitor of Wnt signalling and bone formation, (1,2) has provided a major advance in bone biology. It gives us new insights into the communicating networks among bone cells and, importantly, to new ways of restoring bone once it has been lost. In the current issue of JBMR, Kramer and colleagues complement their earlier demonstration that parathyroid hormone (PTH) inhibits sclerostin expression (3) to show that the anabolic effect of PTH is blunted both in mice overexpressing sclerostin and in SOST null mice. (4) PTH administered by daily injection is the only currently available anabolic therapy for bone. (5,6) While a number of contributing pathways, including direct prodifferentiation (7) and antiapoptotic (8) actions on osteoblasts, as well as couplingrelated activity through the osteoclast, (9) have been proposed, the full mechanism of action of anabolic PTH remains obscure. Another contributory mechanism was introduced by the discovery of sclerostin and its regulation by both PTH and PTH-related protein (PTHrP) via a distal enhancer of the SOST gene. (3,10) The experiments reported by Kramer and colleagues (4) provide further evidence that sclerostin regulation may play a part in PTH anabolic action. Mice overexpressing sclerostin have less bone as a result of decreased bone-formation rate, as described previously. (11) When these mice were treated with a high dose of PTH, sufficient to increase trabecular bone volume (BV/TV) in wild-type mice, no increase in trabecular bone volume was detected despite a robust reduction in sclerostin expression. It is worth noting that even though sclerostin mRNA levels are reduced by PTH in the transgenic model, total sclerostin expression after PTH treatment is still greater than in wild-type mice. This high level of sclerostin expression, the basal phenotype of a mild reduction in bone remodeling, or both impair the effect of PTH on BV/TV. Surprisingly, even though BV/ TV was not increased, all histomorphometric markers of bone formation, as well as the osteoclast surface, were substantially elevated by PTH treatment in the sclerostin transgenic mice to approximately the same extent as that observed in wild-type mice. Thus a question in the sclerostin transgenic model remains as to how PTH can increase bone turnover without altering BV/ TV. Is osteoclast function enhanced? No evidence was obtained for that. An alternative explanation could be that the sclerostin overexpressing mice lay down bone of reduced quality that is easier for osteoclasts to resorb. The quality of bone in the sclerostin overexpressing mouse is not yet known. Resolving this paradox may provide useful information about the interaction between osteoclasts and osteoblasts in the presence of high levels of sclerostin and, presumably, low levels of b-cateninactivated gene transcription.In SOST null mice, as expected from the skeletal abnormalities observed in van Buchem disease and sclerosteosis, (12) trabecular...

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“…In contrast, loss-of-function of LRP5 leads to OPPG with low bone mass 28 , which is similar to the bone phenotype of mice overexpressing Sost 50 . In addition, recent genome-wide SNPbased analyses identified a significant association between bone mineral density and the SOST gene locus [66][67][68] .…”

Section: Sost/sclerostinmentioning

confidence: 99%

New Aspect of Bone Morphogenetic Protein Signaling and Its Relationship with Wnt Signaling in Bone

Kamiya¹

2012

Molecular Interactions

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The −9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPα and FOXA1 binding is associated with osteoporosis

Cited by 51 publications

References 38 publications

Association between Polymorphisms in Sclerostin, Dickkopfs and Secreted Frizzled-Related Protein Genes and Bone Mineral Density in Postmenopausal Korean Women

Association between Polymorphisms in Sclerostin, Dickkopfs and Secreted Frizzled-Related Protein Genes and Bone Mineral Density in Postmenopausal Korean Women

Building bone with a SOST-PTH partnership

New Aspect of Bone Morphogenetic Protein Signaling and Its Relationship with Wnt Signaling in Bone

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