Saint Francis University

About: Saint Francis University is a education organization based out in Loretto, Pennsylvania, United States. It is known for research contribution in the topics: Population & Osteoblast. The organization has 1694 authors who have published 2038 publications receiving 87149 citations.

"Successful aging": effect of subclinical cardiovascular disease.

Abstract: Background Cardiovascular diseases are the primary cause of death in older adults. Among those without clinical disease, high levels of subclinical disease are associated with poor survival. The effect of the extent of subclinical cardiovascular disease on the quality of the remaining years has not been defined. Methods In a longitudinal cohort study, 2932 men and women aged 65 years and older were followed up for 8 years to determine the likelihood of maintaining intact health and functioning. Successful aging was defined as remaining free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease and with intact physical and cognitive functioning. Results Younger age at study entry and a lower extent of subclinical cardiovascular disease were independently associated with the likelihood of maintaining successful aging. In age-stratified summaries, those with subclinical disease had a trajectory of decline similar to subjects 5 years older without subclinical vascular disease. Regression analyses showed that the decline associated with subclinical disease was equivalent to 6.5 (95% confidence interval, 6.4-6.6) years of aging for women and 5.6 (95% confidence interval, 5.4-5.8) years of aging for men. Individual measures of the extent of cardiovascular disease, diabetes mellitus, smoking, and higher C-reactive protein level were also independently predictive of fewer years of successful aging, but none of these factors substantially attenuated the effect of age itself. Conclusions There is a graded relationship between the extent of vascular disease measured noninvasively and the likelihood of maintaining intact health and function. Prevention of subclinical vascular disease may increase the quality and the quantity of years in late life.

A soluble activin Type IIA receptor induces bone formation and improves skeletal integrity

Abstract: Diseases that affect the regulation of bone turnover can lead to skeletal fragility and increased fracture risk. Members of the TGF-superfamily have been shown to be involved in the regulation of bone mass. Activin A, a TGF-� signaling ligand, is present at high levels in bone and may play a role in the regulation of bone metabolism. Here we demonstrate that pharmacological blockade of ligand signaling through the high affinity receptor for activin, type II activin receptor (ActRIIA), by administration of the soluble extracellular domain of ActRIIA fused to a murine IgG2a-Fc, increases bone formation, bone mass, and bone strength in normal mice and in ovariectomized mice with established bone loss. These observations support the development of this pharmacological strategy for the treatment of diseases with skeletal fragility.

Skeletal overexpression of gremlin impairs bone formation and causes osteopenia.

Abstract: Skeletal cells synthesize bone morphogenetic proteins (BMPs) and BMP antagonists. Gremlin, a BMP antagonist, is expressed in osteoblasts and opposes BMP effects on osteoblastic differentiation and function in vitro. However, its effects in vivo are not known. To investigate the actions of gremlin on bone remodeling in vivo, we generated transgenic mice overexpressing gremlin under the control of the osteocalcin promoter. Gremlin transgenics exhibited bone fractures and reduced bone mineral density by 20–30%, compared with controls. Static and dynamic histomorphometry of femurs revealed that gremlin overexpression caused reduced trabecular bone volume and the appearance of woven bone. Polarized light microscopy revealed disorganized collagen bundles at the endosteal cortical surface. Gremlin transgenic mice displayed a 70% decrease in the number of osteoblasts/trabecular area and reduced mineral apposition and bone formation rates. In vivo bromodeoxyuridine labeling and marrow stromal cell cultures demonst...

Glucocorticoid regulation of transforming growth factor beta 1 activity and binding in osteoblast-enriched cultures from fetal rat bone.

Abstract: Transforming growth factor beta (TGF-beta) enhances replication and bone matrix protein synthesis and associates with distinct binding sites in osteoblast-enriched cultures from fetal rat bone. In the organism high levels of or sustained exposure to glucocorticoids alters bone cell activity and decreases bone mass, effects that may be mediated in part by changes in local TGF-beta actions in skeletal tissue. Preexposure of osteoblast-enriched cultures to 100 nM cortisol reduced the stimulatory effects of TGF-beta 1 on DNA and collagen synthesis by 40 to 50%. Binding studies showed that cortisol moderately enhanced total TGF-beta 1 binding, but chemical cross-linking and polyacrylamide gel electrophoretic analysis revealed an increase only within Mr 250,000 (type III) TGF-beta-binding complexes, which are thought to represent extracellular TGF-beta storage sites. In contrast, a decrease in TGF-beta 1 binding was detected in Mr 65,000 (type I) and 85,000 (type II) complexes, which have been implicated as signal-transducing TGF-beta receptors. Our present studies therefore indicate that glucocorticoids can decrease the anabolic effects of TGF-beta 1 in bone, and these may occur in part by a redistribution of its binding toward extracellular matrix storage sites. Alterations of this sort could contribute to bone loss associated with glucocorticoid excess.