Evidence for Altered Canonical Wnt Signaling in the Trabecular Bone of Elderly Postmenopausal Women with Fragility Femoral Fracture

Bolamperti, Simona; Villa, Isabella; Spinello, Alice; Manfredini, Greta; Mrak, Emanuela; Mezzadri, U.; Ometti, Marco; Fraschini, G.; Guidobono, F.; Rubinacci, Alessandro

doi:10.1155/2016/8169614

Cited by 7 publications

(9 citation statements)

References 41 publications

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“…Wnt pathway is a critical regulator of bone formation, thus its disequilibrium could be involved in bone loss and consequent fracture events in OP patients. Bolamperti et al [ 69 ] first analyzed the expression of genes involved in Wnt signaling, osteogenesis and adipogenesis processes in bone tissues derived from 25 women with femoral neck fracture and 29 nonfractured osteoarthritic patients (OA). The results showed a decrease in the expression of genes associated with osteogenesis in the fractured group compared to the OA group.…”

Section: Circulating Mirnas As Potential Biomarkers In Bone Fragilmentioning

confidence: 99%

Circulating miRNAs: A New Opportunity in Bone Fragility

et al. 2020

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Osteoporosis, one of the leading causes of bone fractures, is characterized by low bone mass and structural deterioration of bone tissue, which are associated with a consequent increase in bone fragility and predisposition to fracture. Current screening tools are limited in estimating the proper assessment of fracture risk, highlighting the need to discover novel more suitable biomarkers. Genetic and environmental factors are both implicated in this disease. Increasing evidence suggests that epigenetics and, in particular, miRNAs, may represent a link between these factors and an increase of fracture risk. miRNAs are a class of small noncoding RNAs that negatively regulate gene expression. In the last decade, several miRNAs have been associated with the development of osteoporosis and bone fracture risk, opening up new possibilities in precision medicine. Recently, these molecules have been identified in several biological fluids, and the possible existence of a circulating miRNA (c-miRNA) signature years before the fracture occurrence is suggested. The aim of this review is to provide an overview of the c-miRNAs suggested as promising biomarkers for osteoporosis up until now, which could be helpful for early diagnosis and monitoring of treatment response, as well as fracture risk assessment, in osteoporotic patients.

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Section: Circulating Mirnas As Potential Biomarkers In Bone Fragilmentioning

confidence: 99%

Circulating miRNAs: A New Opportunity in Bone Fragility

et al. 2020

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“…In the study of Bolamperti et al [ 23 ], both groups had comparable BMD. The expression of the WNT pathway activators: WNT3 and WNT10B , was comparable in both groups, similarly as the CTNNB1 , which was consistent with our results.…”

Section: Discussionmentioning

confidence: 98%

“…The use of HRT, reported by almost a half of the participants, could have been responsible for the differences in DKK1 expression versus our results. Bolamperti et al [ 23 ] compared Wnt pathway gene expression in bone samples, collected from patients with osteoporosis and/or osteoarthrosis (OA) that were qualified to hip arthroplasty. Similarly, as in our investigation, the expression of CTNNB1 was in both groups decreased, however, differently than in our experiment, the DKK1 expression was comparable to the reference gene.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Wnt pathway selected gene expression levels in peripheral blood mononuclear cells (PBMCs) of postmenopausal patients with low bone mass

Stuss

Migdalska-Sęk

Brzeziańska-Lasota

et al. 2020

Bosn J of Basic Med Sci

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The purpose of the study was to assess the expression of selected genes of the Wnt pathway: APC, AXIN1, CTNNB1, DKK1, GSK3β, KREMEN1, SFRP1, WNT1 in peripheral blood mononuclear cells (PBMC) of patients, selected in consideration of their BMD (bone mineral density) and the occurrence of low-energy fractures. The study involved 45 postmenopausal women, divided into 4 groups, according to BMD and fracture history. Measurements of laboratory parameters and RNA expression in PBMC cells were carried out in material, collected once at the inclusion visit. The densitometric examination was performed on all participants. In the analysis of the relative expression levels (REL) of the studied genes in the entire population, we observed an overexpression for SFRP1 in 100% of samples and WNT1. In addition, the REL of DKK1, APC, and GSK3β genes were slightly elevated vs. the calibrator. In contrast, CTNNB1 and AXIN1 presented with a slightly decreased RELs. Analysis did not show any significant differences among the groups in the relative gene expression levels (p<0.05) of particular genes. However, we have observed quite numerous interesting correlations between the expression of the studied genes and BMD, the presence of fractures, and laboratory parameters, both in the whole studied population as well as in selected groups. In conclusion, the high level of CTNNB1 expression maintains normal BMD and/or protects against fractures. It also appears that the changes in expression levels of the Wnt pathway genes in PBMCs reflect the expected changes in bone tissue.

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“…The various studies often have different designs and purposes, and therefore are not directly comparable. Sclerostin is a central inhibitor of the Wnt signaling pathway, and various parts of the Wnt signaling system have been associated with bone status in most types of -omics analyses including GWAS, e.g., β-Catenin and DKK1 in proteomics ( 187 ); SOST, DKK1, WIF1, CTNNB1, and WNT5B in transcriptomics ( 193 , 196 ); FZD10, TBL1X, CSNK1E, WNT8A, CSNK1A1L, SFRP4, and SOST in DNA methylation studies ( 221 , 223 ). Also, TGF-β signaling genes ( 187 , 196 , 198 ) and regulators of osteoclast function ( 187 , 197 , 199 , 242 ) have been identified in more than one type of -omics analysis.…”

Section: Overview Of –Omics Data Resources From Human Bone Tissuementioning

confidence: 99%

“…Sclerostin is a central inhibitor of the Wnt signaling pathway, and various parts of the Wnt signaling system have been associated with bone status in most types of -omics analyses including GWAS, e.g., β-Catenin and DKK1 in proteomics ( 187 ); SOST, DKK1, WIF1, CTNNB1, and WNT5B in transcriptomics ( 193 , 196 ); FZD10, TBL1X, CSNK1E, WNT8A, CSNK1A1L, SFRP4, and SOST in DNA methylation studies ( 221 , 223 ). Also, TGF-β signaling genes ( 187 , 196 , 198 ) and regulators of osteoclast function ( 187 , 197 , 199 , 242 ) have been identified in more than one type of -omics analysis. Furthermore, a study of DNaseI hypersensitive sites during osteoblast differentiation identified changes in chromatin and expression of several genes within the Wnt and TGF-β signaling pathways ( 232 ).…”

Section: Overview Of –Omics Data Resources From Human Bone Tissuementioning

confidence: 99%

Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques

Rauner¹,

Foessl

Formosa

et al. 2021

Front. Endocrinol.

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The availability of large human datasets for genome-wide association studies (GWAS) and the advancement of sequencing technologies have boosted the identification of genetic variants in complex and rare diseases in the skeletal field. Yet, interpreting results from human association studies remains a challenge. To bridge the gap between genetic association and causality, a systematic functional investigation is necessary. Multiple unknowns exist for putative causal genes, including cellular localization of the molecular function. Intermediate traits (“endophenotypes”), e.g. molecular quantitative trait loci (molQTLs), are needed to identify mechanisms of underlying associations. Furthermore, index variants often reside in non-coding regions of the genome, therefore challenging for interpretation. Knowledge of non-coding variance (e.g. ncRNAs), repetitive sequences, and regulatory interactions between enhancers and their target genes is central for understanding causal genes in skeletal conditions. Animal models with deep skeletal phenotyping and cell culture models have already facilitated fine mapping of some association signals, elucidated gene mechanisms, and revealed disease-relevant biology. However, to accelerate research towards bridging the current gap between association and causality in skeletal diseases, alternative in vivo platforms need to be used and developed in parallel with the current -omics and traditional in vivo resources. Therefore, we argue that as a field we need to establish resource-sharing standards to collectively address complex research questions. These standards will promote data integration from various -omics technologies and functional dissection of human complex traits. In this mission statement, we review the current available resources and as a group propose a consensus to facilitate resource sharing using existing and future resources. Such coordination efforts will maximize the acquisition of knowledge from different approaches and thus reduce redundancy and duplication of resources. These measures will help to understand the pathogenesis of osteoporosis and other skeletal diseases towards defining new and more efficient therapeutic targets.

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Evidence for Altered Canonical Wnt Signaling in the Trabecular Bone of Elderly Postmenopausal Women with Fragility Femoral Fracture

Cited by 7 publications

References 41 publications

Circulating miRNAs: A New Opportunity in Bone Fragility

Circulating miRNAs: A New Opportunity in Bone Fragility

Assessment of Wnt pathway selected gene expression levels in peripheral blood mononuclear cells (PBMCs) of postmenopausal patients with low bone mass

Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques

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