Low osteocalcin/collagen type I bone gene expression ratio is associated with hip fragility fractures

Rodrigues, Ana Maria; Caetano-Lopes, Joana; Vale, Ana Catarina; Vidal, Bruno; Lopes, Ana Isabel; Aleixo, Inês; Polido-Pereira, Joaquim; Sepriano, Alexandre; Perpétuo, I.P.; Monteiro, Jacinto; Vaz, M. Fátima

doi:10.1016/j.bone.2012.08.129

Cited by 26 publications

(22 citation statements)

References 55 publications

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“…Interestingly, the deformations and bond rupturing of these matrix constituencies appears to be reversible, and only after significant bond rupturing does this behavior progress to diffuse damage, a level of local material disruption that precedes bone microcracks (Fantner et al, 2007(Fantner et al, , 2005. Interestingly, these nanoscale findings are supported by clinical observations that low quantities of both osteocalcin and osteopontin, in relation to local type I collagen, deoxypyridinoline, or calcium levels have been discovered as significant risk predictors in hip fracture patients (Rodrigues et al, 2012;Tanaka et al, 2011).…”

Section: Bone Plasticitymentioning

confidence: 69%

Extracellular matrix networks in bone remodeling

Alford

Kozloff

Hankenson

2015

The International Journal of Biochemistry & Cell Biology

249

225

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Section: Bone Plasticitymentioning

confidence: 69%

Extracellular matrix networks in bone remodeling

Alford

Kozloff

Hankenson

2015

The International Journal of Biochemistry & Cell Biology

249

225

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“…Using literature mining and pathway databases, we found that these five secreted protein signalling pathways were associated with well-known bone related pathways (Figure 5): SPP1, also known as osteopontin, signalled through integrin receptors, activating the NIK-IKK-NF-κB pathway [30,31]. COL1A1 triggered the integrin receptors, enhancing the GRB2-RAS-RAF-MEK-ERK pathway [32]. NT5E catalysed AMP (adenosine monophosphate) to Ado, inducing adenosine signalling, and influencing osteogenic differentiation [33,34].…”

Section: Resultsmentioning

confidence: 99%

Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

Wang

Yang

Sheng

et al. 2016

IJMS

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Adrenocorticotrophin (ACTH)-secreting pituitary adenoma, also known as Cushing disease (CD), is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT). We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1), collagen type I α 1 chain (COL1A1), 5′-nucleotidase ecto (NT5E), HtrA serine peptidase 1 (HTRA1) and angiopoietin 1 (ANGPT1) and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment.

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“…These results are in line with our present findings showing that a decreased serum level of DKK2 was associated with bone fragility fracture, but not with lumbar spine and hip BMD. This may be because osteoblast mineralization disturbances, signalled by low levels of DKK2, lead to bone nanoarchitecture disorganization and fragility, independently of bone mass loss …”

Section: Discussionmentioning

confidence: 99%

“…This may be because osteoblast mineralization disturbances, signalled by low levels of DKK2, lead to bone nanoarchitecture disorganization and fragility, independently of bone mass loss. (42)(43)(44) DKK1 is a key inhibitor of LRP5/6 and of Wnt-b-catenin signaling, and is mainly expressed by osteocytes. It is therefore expected that an increased DKK-1 expression will be associated with a decreased Wnt activity and bone mass.…”

Section: Discussionmentioning

confidence: 99%

Low Serum Levels of DKK2 Predict Incident Low‐Impact Fracture in Older Women

et al. 2019

Self Cite

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There are currently no robust noninvasive markers of fragility fractures. Secreted frizzled related protein‐1 (sFRP‐1), dickkopf‐related protein 1 (DKK1) and DKK2, and sclerostin (SOST) inhibit Wnt signaling and interfere with osteoblast‐mediated bone formation. We evaluated associations of serum levels of sFRP‐1, DKK1, DKK2, and SOST with incident low‐impact fracture and BMD in 828 women aged ≥65 years from EpiDoC, a longitudinal population‐based cohort. A structured questionnaire during a baseline clinical appointment assessed prevalent fragility fractures and clinical risk factors (CRFs) for fracture. Blood was collected to measure serum levels of bone turnover markers and Wnt regulators. Lumbar spine and hip BMD were determined by DXA scanning. Follow‐up assessment was performed through a phone interview; incident fragility fracture was defined by any new self‐reported low‐impact fracture. Multivariate Cox proportional hazard models were used to analyze fracture risk adjusted for CRFs and BMD. During a mean follow‐up of 2.3 ± 1.0 years, 62 low‐impact fractures were sustained in 58 women. A low serum DKK2 level (per 1 SD decrease) was associated with a 1.5‐fold increase in fracture risk independently of BMD and CRFs. Women in the two lowest DKK2 quartiles had a fracture incidence rate of 32 per 1000 person‐years, whereas women in the two highest quartiles had 14 fragility fractures per 1000 person‐years. A high serum sFRP1 level was associated with a 1.6‐fold increase in fracture risk adjusted for CRFs, but not independently of BMD. Serum levels of SOST ( r = 0.191; p = 0.0025) and DKK1( r = −0.1725; p = 0.011) were correlated with hip BMD, but not with incident fragility fracture. These results indicate that serum DKK2 and sFRP1 may predict low‐impact fracture. The low number of incident fractures recorded is a limitation and serum levels of Wnt regulators should be further studied in other populations as potential noninvasive markers of fragility fractures. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Low osteocalcin/collagen type I bone gene expression ratio is associated with hip fragility fractures

Cited by 26 publications

References 55 publications

Extracellular matrix networks in bone remodeling

Extracellular matrix networks in bone remodeling

Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

Low Serum Levels of DKK2 Predict Incident Low‐Impact Fracture in Older Women

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