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Osteoporosis: HELP
Articles by Christopher Vidal
Based on 5 articles published since 2008

Between 2008 and 2019, Christopher Vidal wrote the following 5 articles about Osteoporosis.
+ Citations + Abstracts
1 Article Association Between Circulating Osteogenic Progenitor Cells and Disability and Frailty in Older Persons: The Nepean Osteoporosis and Frailty Study. 2016

Gunawardene, Piumali / Bermeo, Sandra / Vidal, Christopher / Al-Saedi, Ahmed / Chung, Philip / Boersma, Derek / Phu, Steven / Pokorski, Izabella / Suriyaarachchi, Pushpa / Demontiero, Oddom / Duque, Gustavo. ·Musculoskeletal Ageing Research Program, Sydney Medical School Nepean, The University of Sydney, Penrith, New South Wales, Australia. Department of Geriatric Medicine, Nepean Hospital, Penrith, New South Wales, Australia. · Musculoskeletal Ageing Research Program, Sydney Medical School Nepean, The University of Sydney, Penrith, New South Wales, Australia. · Musculoskeletal Ageing Research Program, Sydney Medical School Nepean, The University of Sydney, Penrith, New South Wales, Australia. Department of Geriatric Medicine, Nepean Hospital, Penrith, New South Wales, Australia. gustavo.duque@sydney.edu.au. ·J Gerontol A Biol Sci Med Sci · Pubmed #26525092.

ABSTRACT: Circulating osteogenic progenitor (COP) cells are considered as surrogates of the mesenchymal repository in the body. In this study, we hypothesized that COP cells decrease with age and that lower levels of COP cells are associated with greater frailty and disability in older persons. Using well-established clinical criteria, we quantified physical performance and disability and stratified frailty in a random sample of community-dwelling individuals enrolled in the Nepean Osteoporosis and Frailty (NOF) Study (mean age 82.8; N = 77; 70% female; 27 nonfrail, 23 prefrail, and 27 frail). Percentage of COP cells was quantified by flow cytometry. Logistic regression models estimated the relationship between the percentage of COP cells and prevalent disability, poor physical performance, and frailty. We found that aging is associated with a significant decrease in COP cells (p < .001). Lower percentages of COP cells were associated with disability and poor physical performance (p < .001). Older adults with COP cells in the lower quartile were more likely to be frail (odds ratio 2.65, 95% confidence interval 2.72-3.15, p < .001). In conclusion, COP cells in the circulation decrease with age. Lower percentages of COP cells in late life are associated with prevalent frailty and disability. Further longitudinal studies are needed to understand COP cells as a risk stratifier, biomarker, or therapeutic target and to predict disability in frail older persons.

2 Article Lamin A/C Acts as an Essential Factor in Mesenchymal Stem Cell Differentiation Through the Regulation of the Dynamics of the Wnt/β-Catenin Pathway. 2015

Bermeo, Sandra / Vidal, Christopher / Zhou, Hong / Duque, Gustavo. ·Musculoskeletal Ageing Research Program, Sydney Medical School Nepean, The University of Sydney, Penrith, New South Wales, Australia. · ANZAC Research Institute, The University of Sydney, Concord, New South Wales, Australia. ·J Cell Biochem · Pubmed #25846419.

ABSTRACT: Changes in the expression of lamin A/C, a fibrilar protein of the nuclear envelope, are associated with the cellular features of age-related bone loss. Reduced expression of lamin A/C inhibits osteoblastogenesis while facilitating adipogenic differentiation of mesenchymal stem cells (MSC) in vitro and in vivo. In this study we investigated the regulatory role that lamin A/C plays on the essential elements of the Wnt/β-catenin pathway, which are pivotal in MSC differentiation. Initially, we assessed the effect of lamin A/C gene (LMNA) overexpression on MSC differentiation while compared it to lamin A/C depleted MSC. Osteogenesis and gene expression of osteogenic factors were higher in LMNA-transfected MSC as compared to control. Conversely, adipogenesis and expression of adipogenic factors were significantly lower in LMNA transfected cells. Nuclear β-catenin was significantly higher (∼two fold) in MSC expressing higher levels of LMNA as compared to control with nuclear β-catenin levels being significantly lower (∼ -42%) in siRNA-treated MSC. Luciferase activity for β-catenin-mediated transcriptional activation was significantly higher in cells overexpressing LMNA. These data indicate that MSC overexpressing LMNA have higher osteogenic and lower adipogenic differentiation potential. In conclusion, our studies demonstrate that lamin A/C plays a significant role in the differentiation of both osteoblasts and adipocytes by regulating some of the elements of Wnt/β-catenin signaling during early MSC differentiation.

3 Article The kynurenine pathway of tryptophan degradation is activated during osteoblastogenesis. 2015

Vidal, Christopher / Li, Wei / Santner-Nanan, Brigitte / Lim, Chai K / Guillemin, Gilles J / Ball, Helen J / Hunt, Nicholas H / Nanan, Ralph / Duque, Gustavo. ·Musculoskeletal Ageing Research Program. ·Stem Cells · Pubmed #25186311.

ABSTRACT: The mechanisms involved in the anabolic effect of interferon gamma (IFNγ) on bone have not been carefully examined. Using microarray expression analysis, we found that IFNγ upregulates a set of genes associated with a tryptophan degradation pathway, known as the kynurenine pathway, in osteogenic differentiating human mesenchymal stem cells (hMSC). We, therefore, hypothesized that activation of the kynurenine pathway plays a role in osteoblastogenesis even in the absence of IFNγ. Initially, we observed a strong increase in tryptophan degradation during osteoblastogenesis with and without IFNγ in the media. We next blocked indoleamine 2,3-dioxygenase-1 (IDO1), the most important enzyme in the kynurenine pathway, using a siRNA and pharmacological approach and observed a strong inhibition of osteoblastogenesis with a concomitant decrease in osteogenic factors. We next examined the bone phenotype of Ido1 knockout (Ido1(-/-)) mice. Compared to their wild-type littermates, Ido1(-/-) mice exhibited osteopenia associated with low osteoblast and high osteoclast numbers. Finally, we tested whether the end products of the kynurenine pathway have an osteogenic effect on hMSC. We identified that picolinic acid had a strong and dose-dependent osteogenic effect in vitro. In summary, we demonstrate that the activation of the kynurenine pathway plays an important role during the commitment of hMSC into the osteoblast lineage in vitro, and that this process can be accelerated by exogenous addition of IFNγ. In addition, we found that mice lacking IDO1 activity are osteopenic. These data therefore support a new role for the kynurenine pathway and picolinic acid as essential regulators of osteoblastogenesis and as potential new targets of bone-forming cells in vivo.

4 Article Functional polymorphisms within the TNFRSF11B (osteoprotegerin) gene increase the risk for low bone mineral density. 2011

Vidal, Christopher / Formosa, Robert / Xuereb-Anastasi, Angela. ·DNA Laboratory, Department of Applied Biomedical Science, Faculty of Health Sciences Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta. ·J Mol Endocrinol · Pubmed #21994215.

ABSTRACT: Polymorphisms within the TNFRSF11B gene have been studied and associated with osteoporosis and fracture risk. Osteoprotegerin (OPG), the product of this gene, is a key negative regulator of osteoclastogenesis and is secreted by osteoblasts/stromal cells. A previous study in Maltese postmenopausal women showed positive association of low bone mineral density (BMD) with a polymorphism found within the promoter region of this gene (C950T). In this study, direct DNA sequencing revealed 12 variants with polymorphisms C950T, G1181C and rs4876869 observed to be in strong linkage disequilibrium. The constructed haplotype T-G-T was found to increase the risk for a low BMD, while C-G-T and C-C-C have a protective role; thus, we investigated the functional role of both C950T and rs4876869 in vitro. The promoter region, including the C950T alleles, was amplified by PCR, cloned into pGL3 enhancer vector and transfected into HeLa, COS-7 and RAW264.7 cell lines. After incubation, luciferase activity was measured. The T/C (rs4876869) change was tested for its possible effect on pre-mRNA splicing, using an exon-trapping vector. A statistical significant difference in gene expression was observed between the alleles for T950C, with the T allele showing a lower luciferase expression in all cell lines (P<0.01). For rs4876869, exon skipping was observed for the C allele, while only one transcript harbouring the whole exon was observed for the T allele. Our findings suggest that the T-G-T haplotype might be increasing the risk for osteoporosis due to lower quantities of the full OPG transcript being expressed resulting in a higher bone resorption.

5 Article Effects of a synonymous variant in exon 9 of the CD44 gene on pre-mRNA splicing in a family with osteoporosis. 2009

Vidal, Christopher / Cachia, Adela / Xuereb-Anastasi, Angela. ·Department of Pathology, University of Malta, Medical School, G'Mangia, Malta. ·Bone · Pubmed #19580891.

ABSTRACT: In a previous linkage study, suggestive linkage to osteoporosis was observed in marker D11S1392 on chromosome 11p12. The CD44 gene, found at this locus, was sequenced in one of the families studied. Sequencing all coding regions and promoter in affected and non-affected family members revealed a number of sequence variants, one of which was found to be linked and inherited identical by descent together with the linked STR allele. This G to A variant, which does not cause an amino acid change, was found in exon 9 of the CD44 gene, 32 base pairs upstream from the exon-intron junction. Preliminary analysis using a bioinformatics tool suggested that the presence of the A allele abolished an exon splicing enhancer (ESE) site, thus possibly affecting RNA splicing. It was observed using an exon-trapping vector, that in the presence of the A allele, only one transcript was observed in RAW264.7 cells, as opposed to two transcripts transcribed in the presence of the G allele. These observations suggest that the linked synonymous variant found in exon 9 of the CD44 gene might be increasing susceptibility to osteoporosis in this family by affecting the splicing mechanism.