Association Between Circulating Osteogenic Progenitor Cells and Disability and Frailty in Older Persons: The Nepean Osteoporosis and Frailty Study

Gunawardene, Piumali; Bermeo, Sandra; Vidal, Christopher; Saedi, Ahmed Al; Chung, Philip; Boersma, Derek; Phu, Steven; Pokorski, Izabella; Suriyaarachchi, Pushpa; Demontiero, Oddom; Duque, Gustavo

doi:10.1093/gerona/glv190

Cited by 33 publications

(33 citation statements)

References 37 publications

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“…Purity of sorted OCN-positive cells was >95%. Our group has presented COP cell data previously as a percentage of PBMCs, (19–21) similar to others (22–24) ; however, COP cell data have also been presented as total number of COP cells. (25,26) Therefore, in this study, we present COP cell data both as a percentage of PBMCs and as total number by multiplying % COPs by total PBMC/mL derived from cell counter for each specimen.…”

Section: Methodsmentioning

confidence: 63%

Abnormal Bone Acquisition With Early-Life HIV Infection: Role of Immune Activation and Senescent Osteogenic Precursors

Manavalan

Arpadi

Tharmarajah

et al. 2016

Journal of Bone and Mineral Research

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Chronic immune activation associated with human immunodeficiency virus (HIV) infection may have negative consequences on bone acquisition in individuals infected with HIV early in life. Bone mineral density (BMD) and microarchitecture were characterized in 38 HIV-infected men on antiretroviral therapy (18 perinatally-infected, 20 adolescence-infected) and 20 uninfected men age 20 to 25 years by dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT). Flow cytometry was utilized to measure CD4+/CD8+ activation (HLADR+CD38+) and senescence (CD28−CD57+) and to quantify circulating osteogenic precursor (COP) cells in peripheral blood mononuclear cells using antibodies to RUNX2 and osteocalcin (OCN). Telomere lengths were measured in sorted COP cells using qPCR. DXA-derived areal BMD Z-scores and HRpQCT-derived volumetric BMD (vBMD) measures were lower in HIV-infected than uninfected men. Proportion of activated and senescent CD4+ and CD8+ T cells were higher in HIV-infected than uninfected men. The percentage of COP cells (mean ± SE) was lower in HIV-infected than uninfected (0.19% ± 0.02% versus 0.43% ± 0.06%; p < 0.0001) men, and also lower in perinatally-infected than adolescence-infected men (0.15% ± 0.02% versus 0.22% ± 0.03%; p < 0.04). A higher proportion of COP cells correlated with higher bone stiffness, a measure of bone strength, whereas a higher proportion of activated CD4+ T cells correlated with lower BMD and stiffness and lower proportion of COP cells. T cell activation with HIV-infection was associated with decreased numbers of osteogenic precursors as well as lower peak bone mass and bone strength.

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Section: Methodsmentioning

confidence: 63%

Abnormal Bone Acquisition With Early-Life HIV Infection: Role of Immune Activation and Senescent Osteogenic Precursors

Manavalan

Arpadi

Tharmarajah

et al. 2016

Journal of Bone and Mineral Research

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“…However, understanding the biological impact of low levels of COP cells remained unknown. Therefore, in the Nepean Osteoporosis and Frailty (NOF) study,103 we tested the hypothesis that low %COP levels were associated with frailty and disability. In this study, a random sample of community-dwelling and residential aged-care volunteers aged 65 years and older (mean age 82.8 years; n=77; 70% female; 27 robust, 23 prefrail, and 27 frail) was recruited, with frailty status determined using the Fried et al and Rockwood et al models.…”

Section: Circulating Osteoprogenitor Cells: New Biomarkers For Frailtymentioning

confidence: 99%

<p>Current and emerging biomarkers of frailty in the elderly</p>

Saedi¹,

Feehan²,

Phu³

et al. 2019

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142

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The term "frailty" is used to describe a subset of older adults who appear weaker and more vulnerable than their age-matched counterparts, despite having similar comorbidities, demography, sex, and age. The diagnosis of frailty is usually clinical and based on specific criteria, which are sometimes inconsistent. Therefore, there is an increasing need to identify and validate robust biomarkers for this condition. In this review, we summarize current evidence on the validity and practicality of the most commonly used biomarkers for frailty, while also comparing them with new upcoming strategies to identify this condition.

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“…Closely linked to aging, frailty syndrome is usually suffered by older adults, characterized by exhaustion, unintentional weight loss and a multisystemic function decline. Interestingly, frailty patients have been shown to possess low percentages of circulating osteoprogenitors (COPs) [ 163 ], cells with characteristics of MSCs [ 164 ]. Moreover, a later study proposed lamin A/C as a potential biomarker for this condition, since lamin A/C levels were found to be decreased in COPs from aged individuals suffering frailty [ 165 ].…”

Section: Lamin A/c Dysfunction In Mscs Aging and Bone Diseasementioning

confidence: 99%

Crucial Role of Lamin A/C in the Migration and Differentiation of MSCs in Bone

Alcorta-Sevillano

Macías

Rodrı́guez

et al. 2020

Cells

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Lamin A/C, intermediate filament proteins from the nuclear lamina encoded by the LMNA gene, play a central role in mediating the mechanosignaling of cytoskeletal forces into nucleus. In fact, this mechanotransduction process is essential to ensure the proper functioning of other tasks also mediated by lamin A/C: the structural support of the nucleus and the regulation of gene expression. In this way, lamin A/C is fundamental for the migration and differentiation of mesenchymal stem cells (MSCs), the progenitors of osteoblasts, thus affecting bone homeostasis. Bone formation is a complex process regulated by chemical and mechanical cues, coming from the surrounding extracellular matrix. MSCs respond to signals modulating the expression levels of lamin A/C, and therefore, adapting their nuclear shape and stiffness. To promote cell migration, MSCs need soft nuclei with low lamin A content. Conversely, during osteogenic differentiation, lamin A/C levels are known to be increased. Several LMNA mutations present a negative impact in the migration and osteogenesis of MSCs, affecting bone tissue homeostasis and leading to pathological conditions. This review aims to describe these concepts by discussing the latest state-of-the-art in this exciting area, focusing on the relationship between lamin A/C in MSCs’ function and bone tissue from both, health and pathological points of view.

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Association Between Circulating Osteogenic Progenitor Cells and Disability and Frailty in Older Persons: The Nepean Osteoporosis and Frailty Study

Cited by 33 publications

References 37 publications

Abnormal Bone Acquisition With Early-Life HIV Infection: Role of Immune Activation and Senescent Osteogenic Precursors

Abnormal Bone Acquisition With Early-Life HIV Infection: Role of Immune Activation and Senescent Osteogenic Precursors

<p>Current and emerging biomarkers of frailty in the elderly</p>

Crucial Role of Lamin A/C in the Migration and Differentiation of MSCs in Bone

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