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Osteoporosis: HELP
Articles by Christopher Vidal
Based on 7 articles published since 2010
(Why 7 articles?)
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Between 2010 and 2020, Christopher Vidal wrote the following 7 articles about Osteoporosis.
 
+ Citations + Abstracts
1 Article Treatment with an inhibitor of fatty acid synthase attenuates bone loss in ovariectomized mice. 2019

Bermeo, Sandra / Al Saedi, Ahmed / Vidal, Christopher / Khalil, Mamdouh / Pang, Manhui / Troen, Bruce R / Myers, Damian / Duque, Gustavo. ·Sydney Medical School Nepean, The University of Sydney, Penrith, NSW 2750, Australia; Facultad de Ciencias Básicas y Biomédicas, Universidad Simón Bolívar, Barranquilla, Colombia. · Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St Albans, VIC 3021, Australia; Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St Albans, VIC 3021, Australia. · Sydney Medical School Nepean, The University of Sydney, Penrith, NSW 2750, Australia. · ANZAC Research Institute, Sydney Medical School Concord, The University of Sydney, Concord, NSW 2137, Australia. · Division of Geriatrics and Palliative Medicine, Jacobs School of Medicine and Biomedical Sciences and Research Service, Veterans Affairs Western New York Healthcare System, University at Buffalo, Buffalo, NY, USA. · Sydney Medical School Nepean, The University of Sydney, Penrith, NSW 2750, Australia; Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St Albans, VIC 3021, Australia; Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St Albans, VIC 3021, Australia. Electronic address: gustavo.duque@unimelb.edu.au. ·Bone · Pubmed #30779961.

ABSTRACT: Bone and fat cells have an antagonistic relationship. Adipocytes exert a toxic effect on bone cells in vitro through the secretion of fatty acids, which are synthesized by fatty acid synthase (FAS). Inhibition of FAS in vitro rescues osteoblasts from fat-induced toxicity and cell death. In this study, we hypothesized that FAS inhibition would mitigate the loss of bone mass in ovariectomized (OVX) mice. We treated OVX C57BL/6 mice with cerulenin (a known inhibitor of FAS) for 6 weeks and compared their bone phenotype with vehicle-treated controls. Cerulenin-treated mice exhibited a significant decrease in body weight, triglycerides, leptin, and marrow and subcutaneous fat without changes in serum glucose or calciotropic hormones. These effects were associated with attenuation of bone loss and normalization of the bone phenotype in the cerulenin-treated OVX group compared to the vehicle-treated OVX group. Our results demonstrate that inhibition of FAS enhances bone formation, induces uncoupling between osteoblasts and osteoclasts, and favors mineralization, thus providing evidence that inhibition of FAS could constitute a new anabolic therapy for osteoporosis.

2 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.

3 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.

4 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.

5 Article Mechanisms of palmitate-induced cell death in human osteoblasts. 2013

Gunaratnam, Krishanthi / Vidal, Christopher / Boadle, Ross / Thekkedam, Chris / Duque, Gustavo. ·Ageing Bone Research Program, Sydney Medical School Nepean, The University of Sydney, Penrith, NSW 2750, Australia. ·Biol Open · Pubmed #24285710.

ABSTRACT: Lipotoxicity is an overload of lipids in non-adipose tissues that affects function and induces cell death. Lipotoxicity has been demonstrated in bone cells in vitro using osteoblasts and adipocytes in coculture. In this condition, lipotoxicity was induced by high levels of saturated fatty acids (mostly palmitate) secreted by cultured adipocytes acting in a paracrine manner. In the present study, we aimed to identify the underlying mechanisms of lipotoxicity in human osteoblasts. Palmitate induced autophagy in cultured osteoblasts, which was preceded by the activation of autophagosomes that surround palmitate droplets. Palmitate also induced apoptosis though the activation of the Fas/Jun kinase (JNK) apoptotic pathway. In addition, osteoblasts could be protected from lipotoxicity by inhibiting autophagy with the phosphoinositide kinase inhibitor 3-methyladenine or by inhibiting apoptosis with the JNK inhibitor SP600125. In summary, we have identified two major molecular mechanisms of lipotoxicity in osteoblasts and in doing so we have identified a new potential therapeutic approach to prevent osteoblast dysfunction and death, which are common features of age-related bone loss and osteoporosis.

6 Article Aging and bone loss: new insights for the clinician. 2012

Demontiero, Oddom / Vidal, Christopher / Duque, Gustavo. · ·Ther Adv Musculoskelet Dis · Pubmed #22870496.

ABSTRACT: It is well known that the underlying mechanisms of osteoporosis in older adults are different than those associated with estrogen deprivation. Age-related bone loss involves a gradual and progressive decline, which is also seen in men. Markedly increased bone resorption leads to the initial fall in bone mineral density. With increasing age, there is also a significant reduction in bone formation. This is mostly due to a shift from osteoblastogenesis to predominant adipogenesis in the bone marrow, which also has a lipotoxic effect that affects matrix formation and mineralization. We review new evidence on the pathophysiology of age-related bone loss with emphasis upon the mechanism of action of current osteoporosis treatments. New potential treatments are also considered, including therapeutic approaches to osteoporosis in the elderly that focus on the pathophysiology and potential reversal of adipogenic shift in bone.

7 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.