Rapamycin improves bone mass in high-turnover osteoporosis with iron accumulation through positive effects on osteogenesis and angiogenesis

Bone ◽  
2019 ◽  
Vol 121 ◽  
pp. 16-28 ◽  
Author(s):  
Jiadong Wu ◽  
Aifei Wang ◽  
Xiao Wang ◽  
Guangfei Li ◽  
Peng Jia ◽  
...  
Keyword(s):  
Bone Mass ◽  
Iron Accumulation ◽  
High Turnover ◽  
Positive Effects ◽  
High Turnover Osteoporosis

scholarly journals Krox20/EGR2 deficiency accelerates cell growth and differentiation in the monocytic lineage and decreases bone mass

Blood ◽  
2010 ◽  
Vol 116 (19) ◽  
pp. 3964-3971 ◽  
Author(s):  
Yankel Gabet ◽  
Sanjeev K. Baniwal ◽  
Nathalie Leclerc ◽  
Yunfan Shi ◽  
Alice E. Kohn-Gabet ◽  
...  
Keyword(s):  
Bone Mass ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
High Turnover ◽  
High Turnover Osteoporosis ◽  
Macrophage Colony ◽  
Monocytic Lineage ◽  
Stimulation Of

Abstract Krox20/EGR2, one of the 4 early growth response genes, is a highly conserved transcription factor implicated in hindbrain development, peripheral nerve myelination, tumor suppression, and monocyte/macrophage cell fate determination. Here, we established a novel role for Krox20 in postnatal skeletal metabolism. Microcomputed tomographic analysis of 4- and 8-week-old mice revealed a low bone mass phenotype (LBM) in both the distal femur and the vertebra of Krox20+/− mice. This was attributable to accelerated bone resorption as demonstrated in vivo by increased osteoclast number and serum C-terminal telopeptides, a marker for collagen degradation. Krox20 haploinsufficiency did not reduce bone formation in vivo, nor did it compromise osteoblast differentiation in vitro. In contrast, growth and differentiation were significantly stimulated in preosteoclast cultures derived from Krox20+/− splenocytes, suggesting that the LBM is attributable to Krox20 haploinsufficiency in the monocytic lineage. Furthermore, Krox20 silencing in preosteoclasts increased cFms expression and response to macrophage colony-stimulating factor, leading to a cell-autonomous stimulation of cell-cycle progression. Our data indicate that the antimitogenic role of Krox20 in preosteoclasts is the predominant mechanism underlying the LBM phenotype of Krox20-deficient mice. Stimulation of Krox20 expression in preosteoclasts may present a viable therapeutic strategy for high-turnover osteoporosis.

scholarly journals Gastric Inhibitory Polypeptide as an Endogenous Factor Promoting New Bone Formation after Food Ingestion

2006 ◽  
Vol 20 (7) ◽  
pp. 1644-1651 ◽  
Author(s):  
Katsushi Tsukiyama ◽  
Yuichiro Yamada ◽  
Chizumi Yamada ◽  
Norio Harada ◽  
Yukiko Kawasaki ◽  
...  
Keyword(s):  
Bone Formation ◽  
Intracellular Signaling ◽  
Gastric Inhibitory Polypeptide ◽  
Calcium Deposition ◽  
High Turnover ◽  
Blood Calcium ◽  
Gut Hormone ◽  
High Turnover Osteoporosis ◽  
Meal Ingestion

Abstract Calcium plays a fundamental role as second messenger in intracellular signaling and bone serves as the body’s calcium reserve to tightly maintain blood calcium levels. Calcium in ingested meal is the main supply and inadequate calcium intake causes osteoporosis and bone fracture. Here, we describe a novel mechanism of how ingested calcium is deposited on bone. Meal ingestion elicits secretion of the gut hormone gastric inhibitory polypeptide (GIP) from endocrine K cells in the duodenum. Bone histomorphometrical analyses revealed that bone formation parameters in the mice lacking GIP receptor (GIPR−/−) were significantly lower than those of wild-type (GIPR+/+) mice, and that the number of osteoclasts, especially multinuclear osteoclasts, was significantly increased in GIPR−/− mice, indicating that GIPR−/− mice have high-turnover osteoporosis. In vitro examination showed the percentage of osteoblastic cells undergoing apoptosis to be significantly decreased in the presence of GIP. Because GIPR−/− mice exhibited an increased plasma calcium concentration after meal ingestion, GIP directly links calcium contained in meal to calcium deposition on bone.

Effect of exercise on the development of osteoporosis in adult rats

1989 ◽  
Vol 66 (1) ◽  
pp. 14-19 ◽  
Author(s):  
K. H. Myburgh ◽  
T. D. Noakes ◽  
M. Roodt ◽  
F. S. Hough
Keyword(s):  
Breaking Strength ◽  
Bone Volume ◽  
Moderate Exercise ◽  
High Turnover ◽  
Urinary Hydroxyproline ◽  
Adult Rats ◽  
Normal Bone ◽  
High Turnover Osteoporosis ◽  
Long Evans

The role of moderate exercise in the prevention of high-turnover osteoporosis was investigated by the use of an animal model. The effect of chronic training on gravimetric, mineral, physical, and histological parameters of normal bone was also examined. Fifty-six adult female Long-Evans rats were divided into four groups: sedentary (C) and exercising controls (E) and sedentary (O) and exercising osteoporotics (EO). Exercising animals ran 4 h/wk for 1 yr. Two percent NH4Cl added to drinking water induced osteoporosis as shown by significantly lower femoral density and breaking strength and histomorphometrically quantified tibial trabecular bone volume but a normal mineral-to-matrix ratio in the O rats. The development of high-turnover osteoporosis in O rats was confirmed by significantly higher alkaline phosphatase activity (P less than 0.05), urinary hydroxyproline content (P less than 0.01), resorption surfaces (P less than 0.01), and histological parameters of bone formation (P less than 0.01). Exercise prevented all these biochemical, biophysical, and histological abnormalities in the EO group. Exercise had no influence on the density of normal femurs but tended to increase their breaking strength (by 11%) compared with femurs of C rats (P = 0.11).

scholarly journals Effects of fructans-containing yacon (Smallanthus sonchifoliusPoepp & Endl.) flour on caecum mucosal morphometry, calcium and magnesium balance, and bone calcium retention in growing rats

2007 ◽  
Vol 97 (4) ◽  
pp. 776-785 ◽  
Author(s):  
Alexandre R. Lobo ◽  
Célia Colli ◽  
Eliana P. Alvares ◽  
Tullia M. C. C. Filisetti
Keyword(s):  
Bone Mass ◽  
Bone Mineral ◽  
Peak Load ◽  
Biomechanical Testing ◽  
Biomechanical Properties ◽  
Control Group ◽  
Mineral Density ◽  
Tissue Samples ◽  
Mineral Absorption ◽  
Positive Effects

Yacon roots have been considered a functional food due to the high levels of fructans they contains. In the present study, Ca and Mg balance, bone mass and strength, and caecum mucosal morphometry were evaluated. Growing male Wistar rats (n24) were fedad libitumcontrol diets or diets supplemented with yacon flour (5 or 7·5 % fructooligosaccharides) for 27 d. Mineral balance was evaluated in three periods of 5 d (starting on the 4th, 10th and 16th days). After the rats were killled, the bones were removed and bone mineral density was measured. Ca analyses were performed on left femurs and tibias and biomechanical testing on right femurs. The caecum was removed and tissue samples were collected for histological analysis. Caecal histology changed noticeably in rats fed yacon flour: there was an increase in the depth and number of total and bifurcated crypts as well. Yacon flour consumption significantly (P < 0·05) resulted in a positive Ca and Mg balance, leading to higher values of bone mineral retention and biomechanical properties (peak load and stiffness) when compared to the control group. The positive effects on mineral intestinal absorption, bone mass and biomechanical properties showed an important role of yacon roots in the maintenance of healthy bones. The increased number of bifurcating crypts might be related to the higher mineral absorption caused by the enlargement of the absorbing surface in the large intestine of the animals.

scholarly journals Iron accumulation deteriorated bone loss in estrogen-deficient rats

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Lu-lin Liu ◽  
Gong-wen Liu ◽  
Hui Liu ◽  
Kai Zhao ◽  
You-jia Xu
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Mass ◽  
Serum Iron ◽  
Sham Group ◽  
Iron Accumulation ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Ovx Rats ◽  
Ferric Ammonium

Abstract Background Postmenopausal osteoporosis is characterized by an imbalance of bone resorption exceeding bone formation, resulting in a net loss of bone mass. Whether a menopause-related excess of iron contributes to the development of postmenopausal osteoporosis has remained unresolved due to a lack of an appropriate animal model. This study aimed to explore the effects of iron accumulation in bone mass in estrogen-deficient rats. Methods In the present study, ovariectomy (OVX) was performed in female rats and the changes of iron metabolism and some related modulated genes were detected. Ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. Moreover, micro-CT was performed to assess the bone microarchitecture in sham group, OVX, and FAC groups. Histological detection of iron in liver was assessed by Perl’s staining. The expressions of β-CTX and osteocalcin were assessed by ELISA. Results It was found that serum iron decreased after OVX. It was found that the expressions of Hepcidin in liver and Fpn, DMT-1 in duodenum significantly decreased at transcriptional level in OVX group than sham group. However, no difference existed in the expression of DMT-1. Then, ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. The FAC group manifested significant iron accumulation by increased serum iron and hepatic iron content. In addition, FAC treatment accelerated bone loss and decreased BMD and biomechanics in OVX rats. Moreover, bone biomarker β-CTX rather than osteocalcin increased significantly in FAC groups than OVX group. Conclusions In conclusion, no iron accumulation occurred in OVX rats. Furthermore, iron accumulation could further deteriorate osteopenia through enhanced bone resorption.

scholarly journals IMPACTS OF NEOLIBERALISM ON HOSPITAL NURSING WORK

2015 ◽  
Vol 24 (3) ◽  
pp. 646-653 ◽  
Author(s):  
Francisco Gleidson de Azevedo Gonçalves ◽  
Norma Valéria Dantas de Oliveira Souza ◽  
Regina Célia Gollner Zeitoune ◽  
Gabriela Fontes Pessanha Leite Adame ◽  
Sonia Maria Pereira do Nascimento
Keyword(s):  
Structured Interview ◽  
Treatment Technique ◽  
Exploratory Research ◽  
Process Of Care ◽  
High Turnover ◽  
Positive Effects ◽  
Hospital Nursing ◽  
Employment Conditions ◽  
Qualitative Descriptive ◽  
Negative Impacts

ABSTRACTThis study aims to describe and analyze the implications of the neoliberal model in the dynamics of hospital work, in the view of the nursing workers. It is a qualitative, descriptive and exploratory research. The scenario is a teaching hospital, and the subjects are 17 nursing workers. The collection took place in July and August 2011, through a semi-structured interview. The data treatment technique was the content analysis. The results show that neoliberalism in hospital nursing work entails several negative impacts, which focus on the inappropriate distribution of material resources, as well as the heavy use of technologies in the process of care. There is also a high turnover of workers contracted due to low wages and precarious employment conditions. We conclude that the neoliberal model has both negative and positive effects. It is considered important to approach this subject in training courses of future nursing staff.

scholarly journals ERα expression in T lymphocytes is dispensable for estrogenic effects in bone

2018 ◽  
Vol 238 (2) ◽  
pp. 129-136 ◽  
Author(s):  
K L Gustafsson ◽  
K H Nilsson ◽  
H H Farman ◽  
A Andersson ◽  
V Lionikaite ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Bone Mass ◽  
Estrogen Receptor Alpha ◽  
Estrogen Treatment ◽  
Target Cells ◽  
Mineral Density ◽  
Littermate Control ◽  
Female Mice ◽  
Positive Effects ◽  
Estrogenic Regulation

Estrogen treatment has positive effects on the skeleton, and we have shown that estrogen receptor alpha (ERα) expression in cells of hematopoietic origin contributes to a normal estrogen treatment response in bone tissue. T lymphocytes are implicated in the estrogenic regulation of bone mass, but it is not known whether T lymphocytes are direct estrogen target cells. Therefore, the aim of this study was to determine the importance of ERα expression in T lymphocytes for the estrogenic regulation of the skeleton using female mice lacking ERα expression specifically in T lymphocytes (Lck-ERα−/−) and ERαflox/flox littermate (control) mice. Deletion of ERα expression in T lymphocytes did not affect bone mineral density (BMD) in sham-operated Lck-ERα−/− compared to control mice, and ovariectomy (ovx) resulted in a similar decrease in BMD in control and Lck-ERα−/− mice compared to sham-operated mice. Furthermore, estrogen treatment of ovx Lck-ERα−/− led to an increased BMD that was indistinguishable from the increase seen after estrogen treatment of ovx control mice. Detailed analysis of both the appendicular (femur) and axial (vertebrae) skeleton showed that both trabecular and cortical bone parameters responded to a similar extent regardless of the presence of ERα in T lymphocytes. In conclusion, ERα expression in T lymphocytes is dispensable for normal estrogenic regulation of bone mass in female mice.

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