Aging alters the skeletal response to disuse in the rat

Perrien, Daniel S.; Akel, Nisreen; Dupont‐Versteegden, Esther E.; Skinner, Robert A.; Siegel, Eric R.; Suva, Larry J.; Gaddy, Dana

doi:10.1152/ajpregu.00302.2006

Cited by 59 publications

(45 citation statements)

References 68 publications

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“…A minimum of 25 fields in the proximal tibia were evaluated. Static measurements of osteoblast and osteoclast parameters were obtained as described previously 27,28 and reported using the terminology recommended by the Histomorphometry Nomenclature Committee of American Society for Bone and Mineral Research. 29 …”

Section: Bone Histomorphometrymentioning

confidence: 99%

Platelet Dysfunction and a High Bone Mass Phenotype in a Murine Model of Platelet-Type von Willebrand Disease

Suva

Hartman

Dilley

et al. 2008

The American Journal of Pathology

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110

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The platelet glycoprotein Ib-IX receptor binds surfacebound von Willebrand factor and supports platelet adhesion to damaged vascular surfaces. A limited number of mutations within the glycoprotein Ib-IX complex have been described that permit a structurally altered receptor to interact with soluble von Willebrand factor, and this is the molecular basis of platelet-type von Willebrand disease. We have developed and characterized a mouse model of platelet-type von Willebrand disease (G233V) and have confirmed a platelet phenotype mimicking the human disorder. The mice have a dramatic increase in splenic megakaryocytes and splenomegaly. Recent studies have demonstrated that hematopoetic cells can influence the differentiation of osteogenic cells. Thus, we examined the skeletal phenotype of mice expressing the G233V variant complex. At 6 months of age, G233V mice exhibit a high bone mass phenotype with an approximate doubling of trabecular bone volume in both the tibia and femur. Serum measures of bone resorption were significantly decreased in G233V animals. With decreased bone resorption, cortical thickness was increased, medullary area decreased, and consequently, the mechanical strength of the femur was significantly increased. Using ex vivo bone marrow cultures, osteoclast-specific staining in the G233V mutant marrow was diminished, whereas osteoblastogenesis was unaffected. These studies provide new insights into the relationship between the regulation of megakaryocytopoiesis and bone mass. (Am J

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Section: Bone Histomorphometrymentioning

confidence: 99%

Platelet Dysfunction and a High Bone Mass Phenotype in a Murine Model of Platelet-Type von Willebrand Disease

Suva

Hartman

Dilley

et al. 2008

The American Journal of Pathology

Self Cite

110

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“…34 This accumulation seems to be independent of estrogen, because bone marrow fat appears in bone even when estrogen levels are still normal, during the third and fourth decade of life. 35 Additionally, mice lacking estrogen receptors do not display higher levels of adiposity within their bone marrow than do wild-type mice. 36 Therefore, aging per se, independent of hormonal changes, appears to contribute significantly to bone marrow adipogenesis, raising the possibility that senile osteoporosis is a type of lypotoxic disease.…”

Section: Aging and Bonementioning

confidence: 99%

Understanding the Mechanisms of Senile Osteoporosis: New Facts for a Major Geriatric Syndrome

Duque

Troen

2008

J American Geriatrics Society

133

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Knowledge of the underlying mechanisms of osteoporosis in older adults has significantly advanced in recent years. There is an acute loss of bone mineral density in the peri-menopausal period, followed by a more 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. This study reviews new evidence on the pathophysiology of senile osteoporosis, with emphasis upon the mechanism of action of current osteoporosis treatments. New potential treatments are also considered, including therapeutic approaches to osteoporosis in elderly people that focus on the pathophysiology and potential reversal of the adipogenic shift in bone.

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“…In addition, aging is associated with increased cellular senescence and changes in cellular phenotype that result in cells with decreased matrix synthesis capacity and/or altered matrix production (1)(2)(3)(4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Differential Response of Encapsulated Nucleus Pulposus and Bone Marrow Stem Cells in Isolation and Coculture in Alginate and Chitosan Hydrogels

Naqvi

Buckley

2015

Tissue Engineering Part A

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Cell-based therapies may hold significant promise for the treatment of early stage degeneration of the intervertebral disc (IVD). Given their propensity to proliferate and ability to form multiple tissue types, mesenchymal stem cells (MSCs) have been proposed as a potential cell source to promote repair of the nucleus pulposus (NP). However, for any successful cell-based therapy a carrier biomaterial may be essential for targeted delivery providing key biophysical and biochemical cues to facilitate differentiation of MSCs. Two widely used biomaterials for NP regeneration are chitosan and alginate. The primary objective of this study was to assess the influence of alginate and chitosan hydrogels on bone marrow (BM) MSCs and NP cells in isolation or in co-culture. A secondary objective of this study was to investigate co-culture seeding density effects of BM and NP cells and simultaneously explore which cell type is responsible for matrix formation in a co-cultured environment. Porcine NP and BM cells were encapsulated in alginate and chitosan hydrogels separately at two seeding densities (4x10 6 and 8x10 6 cells/ml) or in co-culture (1:1, 8 x10 6 cells/ml). Constructs (diameter:5mm, height:3mm) were maintained under IVD-like conditions (low-glucose, low (5%) oxygen) with or without TGF-β3 supplementation for 21 days. Results demonstrated differential viability depending on hydrogel type. NP cells remained viable in both biomaterial types whereas BM viability was diminished in chitosan.Furthermore, hydrogel type was found to regulate sGAG and collagen accumulation.Specifically, alginate better supports sGAG accumulation and collagen type II deposition for both NP and BM cell types compared to chitosan. Having identified that alginate more readily supports cell viability and matrix accumulation we further explored additional effects of seeding density ratios (NP: BM -1:1, 1:2) for co-culture studies. Interestingly, in coculture conditions, the BM cell population declined in number while NP cells increased indicating that MSCs may in fact be signalling NP cells to proliferate rather than contributing to matrix formation. These findings provide exciting new insights on the potential of MSCs for NP tissue regeneration strategies.

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Aging alters the skeletal response to disuse in the rat

Cited by 59 publications

References 68 publications

Platelet Dysfunction and a High Bone Mass Phenotype in a Murine Model of Platelet-Type von Willebrand Disease

Platelet Dysfunction and a High Bone Mass Phenotype in a Murine Model of Platelet-Type von Willebrand Disease

Understanding the Mechanisms of Senile Osteoporosis: New Facts for a Major Geriatric Syndrome

Differential Response of Encapsulated Nucleus Pulposus and Bone Marrow Stem Cells in Isolation and Coculture in Alginate and Chitosan Hydrogels

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