scholarly journals The effect of moderately and severely restricted dietary magnesium intakes on bone composition and bone metabolism in the rat

1999 ◽  
Vol 82 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Annette Creedon ◽  
Albert Flynn ◽  
Kevin Cashman
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Development ◽  
Dry Weight ◽  
Male Rats ◽  
Average Weight ◽  
Mrna Levels ◽  
Adequate Diet ◽  
Wistar Strain ◽  
Restricted Group

Forty 3-week-old male rats, Wistar strain, average weight 59 g, were randomized by weight into five groups of eight rats each. Three groups were fedad libitumon a semi-purified diet containing (per kg) 400 (adequate), 200 (moderately Mg-restricted) or 20 (severely Mg-restricted) mg Mg for 3 weeks while two groups were pair-fed with the Mg-adequate diet in the same quantities as those consumed by the two Mg-restricted groups respectively. While weight gains and food conversion efficiency values for the Mg-restricted groups were similar to those of the corresponding pair-fed control groups, serum and kidney Mg, and femoral dry weight were reduced by 70, 7 and 9 % respectively in the severely Mg-restricted group and were unaffected in the moderately Mg-restricted group. Significant reductions were observed in urinary pyridinoline (Pyr) (by 44 and 34 %) and deoxypyridinoline (Dpyr) levels (by 40 and 33 %) (markers of bone resorption), serum osteocalcin levels (by 46 and 28 %) (marker of bone formation), femoral Mg levels (by 52 and 14 %) and osteocalcin mRNA levels (by 46 and 22 %) compared with the corresponding pair-fed controls, in the severely and moderately Mg-restricted groups respectively, and these reductions, except for those in urinary Pyr and Dpyr, were more marked in the severely Mg-restricted group. Femoral Ca and P concentrations were unaffected by dietary Mg restriction. These results show that not only severe but also moderate dietary restriction of Mg over 21 d results in qualitative changes in bone (i.e. reduced Mg concentration) as well as in aberrant bone turnover in young growing rats (i.e. severely depressed rates of bone formation and bone resorption), which may impair bone development and bone strength.

scholarly journals The effect of calcium intake on bone composition and bone resorption in the young growing rat

2001 ◽  
Vol 86 (4) ◽  
pp. 453-459 ◽  
Author(s):  
Annette Creedon ◽  
Kevin D. Cashman
Keyword(s):  
Bone Resorption ◽  
Bone Mineral ◽  
Dry Weight ◽  
Female Rats ◽  
Wistar Strain ◽  
Restricted Group ◽  
Growing Rat ◽  
Old Rats ◽  
Bone Mineral Accrual ◽  
Recommended Level

A low Ca intake by both rats and man increases bone resorption, decreases bone mass and increases the risk of osteoporosis. The skeletal effect of high Ca intakes is less clear, particularly during periods of bone mineral accrual. Twenty-four female 5-week-old rats, Wistar strain, were randomized by weight into three groups of eight rats each and fedad libituma semi-purified diet containing 2 (Ca-restricted), 5 (normal) or 20 (Ca-supplemented) g Ca/kg for 3 weeks. When compared with the normal Ca diet, urinary Ca excretion was unaffected by the dietary restriction of Ca for 3 weeks, but was greater (P<0·001) in Ca-supplemented rats. Urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) levels were significantly greater during weeks 2 (PyrP<0·05, DpyrP<0·001) and 3 (PyrP<0·01, Dpyr,P<0·001) of dietary Ca restriction, but were unaffected by Ca supplementation. Femoral dry weight and the concentration of Mg and P in femora were unaffected by dietary Ca concentration. Femoral Ca concentration was reduced (P<0·05) in the Ca-restricted group compared with the other two groups. In conclusion, these results suggest that increasing dietary Ca intake, well above the recommended level, had no effect on bone mineral composition or bone resorption (as assessed with urinary pyridinium crosslinks) in young growing female rats. In addition, these results confirm the findings of previous studies which have shown that bone Ca content in young growing rats was reduced by dietary Ca restriction and that this reduction results, at least in part, from an increased rate of bone resorption.

The effect of bovine whey protein on ectopic bone formation in young growing rats

2003 ◽  
Vol 90 (3) ◽  
pp. 557-564 ◽  
Author(s):  
Owen Kelly ◽  
Siobhan Cusack ◽  
Kevin D. Cashman
Keyword(s):  
Bone Formation ◽  
Bone Metabolism ◽  
Whey Protein ◽  
Bone Mineral ◽  
Ectopic Bone Formation ◽  
Male Rats ◽  
Mrna Levels ◽  
Growing Rats ◽  
Ectopic Bone ◽  
Igf I

The beneficial effect of bovine whey protein (WP) on bone metabolism has been shown in adult human subjects and ovariectomised rats. However, its effect on bone formation in earlier life, particularly during periods of bone mineral accrual, has not been investigated. Twenty-one male rats (4 weeks old, Wistar strain) were randomised by weight into three groups of seven rats each and fedad libitumon a semi-purified low-Ca diet (3·0 g Ca/kg diet) containing 0 (control), 10 (diet WP1) or 20 (diet WP2) g bovine WP/kg for 47 d. On day 34 of the dietary intervention, all rats had two gelatine capsules containing demineralised bone powder implanted subcutaneously in the thorax region (a well-establishedin vivomodel of ectopic bone formation). At 14 d after implantation, alkaline phosphatase activity (reflective of bone formation) in the bone implants from animals fed WP1 and -2 diets was almost 2-fold (P<0·01) that of control animals. Insulin-like growth factor (IGF)-I mRNA levels were about 3-fold (P<0·05) higher in implants from animals fed the WP diets compared with those from control animals. Serum- and urine-based biomarkers of bone metabolism and bone mineral composition in intact femora were unaffected by WP supplementation. In conclusion, the present findings suggest that bovine WP can enhance the rate of ectopic bone formation in young growing rats fed a Ca-restricted diet. This effect may be mediated by an increased synthesis of IGF-I in growing bone. The effect of WP on bone formation warrants further investigation.

Disuse osteopenia is accompanied by downregulation of gene expression for bone proteins in growing rats

2006 ◽  
Vol 263 (6) ◽  
pp. E1029-E1034
Author(s):  
G. K. Wakley ◽  
J. S. Portwood ◽  
R. T. Turner
Keyword(s):  
Bone Resorption ◽  
Sciatic Nerve ◽  
Bone Formation ◽  
Type I ◽  
Mrna Levels ◽  
Nerve Section ◽  
Bone Formation Rate ◽  
Growing Rats ◽  
Bone Proteins ◽  
Sciatic Neurectomy

Unilateral sciatic neurectomy (USN) resulted in cortical osteopenia in tibiae from the sciatic nerve-sectioned limb of growing rats. The bone deficit resulted from decreased periosteal addition; there were no changes in the indexes of bone resorption. The periosteal bone formation rate was reduced in the nerve-sectioned limb within 7 days of sciatic neurectomy, and this decrease persisted for at least 56 days. Steady-state mRNA levels for bone proteins were determined in periosteum isolated from tibiae and femurs 7 and 14 days after sciatic nerve section. Nerve section resulted in decreased levels of mRNA for osteocalcin, alkaline phosphatase, and possibly the prepro-alpha (I)-subunit of type I collagen (collagen). The effects were more pronounced in tibiae than femurs, corresponding to the greater degree of immobility induced by USN in the former bone. The results demonstrate that decreased bone formation precedes establishment of disuse cortical osteopenia in growing rats with no evidence for a change in bone resorption. Furthermore, the decreased bone formation is associated with, and may be due to, reduced mRNA levels for matrix proteins and other important bone proteins.

The Estimation of Magnesium in Plasma, Muscle and Bone, by Atomic Absorption Spectrophotometry

1969 ◽  
Vol 15 (10) ◽  
pp. 979-996 ◽  
Author(s):  
B J Hunt
Keyword(s):  
Atomic Absorption ◽  
Dry Weight ◽  
Magnesium Content ◽  
Atomic Absorption Spectrophotometry ◽  
Sampling Procedure ◽  
Mean Value ◽  
Male Rats ◽  
Average Weight ◽  
The Mean ◽  
Normal Men

Abstract The use of the EEL 140 atomic absorption spectrophotometer for the determination of magnesium in plasma, skeletal muscle, and bone is described together with an examination of the pattern of chemical interference in each type of sample. The sampling procedure and preparation of each kind of sample for analysis is detailed, and recovery studies on plasma bone and muscle are presented. The mean value for plasma magnesium in 42 normal men and women was 2.16 mg/100 ml ± SD of 0.08. For 30 male Wistar strain rats, the plasma value was 2.10 mg/100 ml ± SD of 0.18. In 15 normal postmortem human muscle samples, the mean magnesium content was found to be 93 mg/100 g of dry muscle, the series range being between 83 and 101 mg/100 g. The comparable value in 49 male rats was 125 mg/100 g dry weight ± SD 1.8. Bone magnesium in femur diaphysis of 20 male rats (average weight 200 g) was 563 mg/100 g dry weight ± SD 12.7. It is concluded that this instrument, when operated in the manner suggested in our study, is technically easy to use, and gives precise, sensitive, and reproducible results for magnesium in a variety of biologic material.

Myeloma Cells Suppress Osteoblast Differentiation by Secreting a Soluble Wnt Inhibitor, sFRP-2.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2356-2356 ◽  
Author(s):  
Takashi Oshima ◽  
Masahiro Abe ◽  
Jin Asano ◽  
Tomoko Hara ◽  
Kenichi Kitazoe ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Osteoblast Differentiation ◽  
Wnt Signaling Pathway ◽  
Bone Destruction ◽  
Nodule Formation ◽  
Mrna Levels

Abstract Multiple myeloma (MM), a malignancy of plasma cells, develops in the bone marrow, and generates devastating bone destruction. Along with enhanced bone resorption, clinical evidence has also suggested suppression of bone formation as a contributing factor to the bone loss in MM. In contrast to recent understanding on mechanisms of osteolysis enahnced in MM, little is known about factors responsible for impaired bone formation. A canonical Wingless-type (Wnt) signaling pathway has recently been shown to play a critical role in osteoblast differentiation. Therefore, in the present study, we aimed to clarify mechanisms of suppression of osteoblast differentiation by MM cells with a particular focus on a canonical Wnt signaling pathway. Because several secreted Frizzled related protein (sFRP) and DKK family members are known as soluble Wnt antagonists, we first examined the expression of sFRP-1, 2 and 3 and DKK-1 in MM cell lines including U266, RPMI8226 and ARH77. All cell lines expressed sFRP-2 and sFRP-3 mRNA observed by RT-PCR. However, sFRP-1 was not expressed in any cell line, and Dkk-1 was expressed only in U266 cells at mRNA levels. We next conducted Western blot analyses for these factors and detected only sFRP-2 in immunoprecipitants of conditioned media as well as cell lysates of all these cell lines. However, no other factors were found at protein levels. Furthermore, sFRP-2 mRNA and protein expression was detected in most MM cells from patients with advanced or terminal stages of MM with bone destruction including plasma cell leukemia (3/4 and 8/10, respectively). In order to examine a biological role for sFRP-2, we added recombinant sFRP-2 to MC3T3-E1 cell culture together with BMP-2. Exogenous sFRP-2 partially suppressed alkaline phosphatase activity but almost completely mineralized nodule formation enhanced by BMP-2. Furthermore, sFRP-2 immunodepletion significantly restored mineralized nodule formation in MC3T3-E1 cells suppressed by RPMI8226 and ARH77 CM. These results suggest that sFRP-2 alone is able to suppress osteoblast differentiation induced by BMP-2 and that MM cell-derived sFRP-2 is among predominant factors responsible for defective bone formation in MM. Because MM cell-derived factors such as DKK-1, IGF-BP4 and IL-3 other than sFRP-2 have been implicated as an inhibitor of osteoblast differentiation, sFRP-2 may act alone or in combination with such other factors to potently suppress bone formation in MM. Taken together, MM cells may cause an imbalance of bone turnover with enhanced osteoclastic bone resorption and concomitantly suppressed bone formation, which leads to devastating destruction and a rapid loss of bone.

Disuse osteopenia is accompanied by downregulation of gene expression for bone proteins in growing rats

1992 ◽  
Vol 263 (6) ◽  
pp. E1029-E1034 ◽  
Author(s):  
G. K. Wakley ◽  
J. S. Portwood ◽  
R. T. Turner
Keyword(s):  
Bone Resorption ◽  
Sciatic Nerve ◽  
Bone Formation ◽  
Type I ◽  
Mrna Levels ◽  
Nerve Section ◽  
Bone Formation Rate ◽  
Growing Rats ◽  
Bone Proteins ◽  
Sciatic Neurectomy

Unilateral sciatic neurectomy (USN) resulted in cortical osteopenia in tibiae from the sciatic nerve-sectioned limb of growing rats. The bone deficit resulted from decreased periosteal addition; there were no changes in the indexes of bone resorption. The periosteal bone formation rate was reduced in the nerve-sectioned limb within 7 days of sciatic neurectomy, and this decrease persisted for at least 56 days. Steady-state mRNA levels for bone proteins were determined in periosteum isolated from tibiae and femurs 7 and 14 days after sciatic nerve section. Nerve section resulted in decreased levels of mRNA for osteocalcin, alkaline phosphatase, and possibly the prepro-alpha (I)-subunit of type I collagen (collagen). The effects were more pronounced in tibiae than femurs, corresponding to the greater degree of immobility induced by USN in the former bone. The results demonstrate that decreased bone formation precedes establishment of disuse cortical osteopenia in growing rats with no evidence for a change in bone resorption. Furthermore, the decreased bone formation is associated with, and may be due to, reduced mRNA levels for matrix proteins and other important bone proteins.

Estrogen has rapid tissue-specific effects on rat bone

1999 ◽  
Vol 86 (6) ◽  
pp. 1950-1958 ◽  
Author(s):  
R. T. Turner ◽  
L. S. Kidder ◽  
M. Zhang ◽  
S. A. Harris ◽  
K. C. Westerlind ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Resorption ◽  
Bone Formation ◽  
Time Course ◽  
Bone Matrix ◽  
Matrix Proteins ◽  
Mrna Levels ◽  
Rnase Protection ◽  
Tissue Specific ◽  
Signaling Peptides

The decrease in cancellous bone formation after estrogen treatment is generally thought to be coupled with a prior decrease in bone resorption. To test the possibility that estrogen has rapid tissue-specific actions on bone metabolism, we determined the time course (1–32 h) effects of diethylstilbestrol on steady-state mRNA levels for immediate-response genes, extracellular matrix proteins, and signaling peptides in the proximal tibial metaphysis and uterus by using Northern blot and RNase protection assays. The regulation of signaling peptides by estrogen, although tissue specific, followed a similar time course in bone and uterus. The observed rapid decreases in expression of insulin-like growth factor I, a growth factor associated with bone formation; decreases in mRNA levels for bone matrix proteins; evidence for reduced bone matrix synthesis; failure to detect rapid increases in mRNA levels for signaling peptides implicated in mediating the inhibitory effects of estrogen on bone resorption (interleukin-1 and -6) as well as other cytokines that can increase bone resorption; and the comparatively long duration of the bone remodeling cycle in rats indicate that estrogen can decrease bone formation by a mechanism that does not require a prior reduction in bone resorption.

scholarly journals Effects of cortisol on the expression of interleukin-6 and interleukin-1 beta in human osteoblast-like cells

1998 ◽  
Vol 156 (1) ◽  
pp. 107-114 ◽  
Author(s):  
D Swolin-Eide ◽  
C Ohlsson
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Culture Medium ◽  
Interleukin 1 ◽  
Control Culture ◽  
Maximum Effect ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Human Osteoblast ◽  
Dose Dependent

High levels of glucocorticoids are believed to alter bone remodeling by decreasing bone formation and increasing bone resorption. It has been suggested that different cytokines, like interleukin-6 (IL-6) and interleukin-1 (IL-1), are involved in bone resorption by activating immature osteoclasts, and some studies indicate that IL-6 promotes bone formation by a mitogenic effect on osteoblasts. The aim of the present investigation was to study whether cortisol regulates the expression of IL-6 and IL-1 beta in human osteoblast-like cells. A high dose of cortisol (10(-7)M) decreased, as expected, the C-terminal propeptide of type I collagen released into the culture medium. The IL-6 mRNA levels and IL-6 protein released into the culture medium were also decreased by cortisol in a dose-dependent manner. The maximum effect was seen at 1 microM cortisol (mRNA 23.1 +/- 7.9% of control culture; protein 28.2 +/- 8.3% of control culture). The decrease in IL-6 mRNA levels was apparent 4 h after the addition of cortisol and was still present 20 h later. The decrease in IL-6 protein released into the culture medium was seen 20 h later than the decrease in IL-6 mRNA levels. The production of IL-1 beta protein released into the culture medium was decreased in a dose-dependent manner after the addition of cortisol with a maximum effect at 1 microM. The effect of cortisol on IL-1 beta protein released into the culture medium was seen 16 h after the addition of cortisol. To summarize, cortisol decreases the expression of IL-6 as well as IL-1 beta in human osteoblast-like cells.

Effect of gender on bone turnover in adult rats during simulated weightlessness

2003 ◽  
Vol 95 (5) ◽  
pp. 1775-1780 ◽  
Author(s):  
T. E. Hefferan ◽  
G. L. Evans ◽  
S. Lotinun ◽  
M. Zhang ◽  
E. Morey-Holton ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Bone Area ◽  
Simulated Weightlessness ◽  
Trabecular Separation ◽  
Trabecular Number

Prologned spaceflight results in bone loss in astronauts, but there is considerable individual variation. The goal of this rat study was to determine whether gender influences bone loss during simulated weightlessness. Six-month-old Fisher 344 rats were hindlimb unweighted for 2 wk, after which the proximal tibiae were evaluated by histomorphometry. There were gender differences in tibia length, bone area, cancellous bone architecture, and bone formation. Compared with female rats, male rats had an 11.6% longer tibiae, a 27.8% greater cortical bone area, and a 37.6% greater trabecular separation. Conversely, female rats had greater cortical (316%) and cancellous (145%) bone formation rates, 28.6% more cancellous bone, and 30% greater trabecular number. Hindlimb unweighting resulted in large reductions in periosteal bone formation and mineral apposition rate in both genders. Unweighting also caused cancellous bone loss in both genders; trabecular number was decreased, and trabecular separation was increased. There was, however, no change in trabecular thickness in either gender. These architectural changes in cancellous bone were associated with decreases in bone formation and steady-state mRNA levels for bone matrix proteins and cancellous bone resorption. In conclusion, there are major gender-related differences in bone mass and turnover; however, the bone loss in hindlimb unweighted adult male and female rats appears to be due to similar mechanisms.

scholarly journals Triazolopyrimidine (Trapidil), a Platelet-Derived Growth Factor Antagonist, Inhibits Parathyroid Bone Disease in an Animal Model for Chronic Hyperparathyroidism

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 2000-2007 ◽  
Author(s):  
Sutada Lotinun ◽  
Jean D. Sibonga ◽  
Russell T. Turner
Keyword(s):  
Growth Factor ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Disease ◽  
Platelet Derived Growth Factor ◽  
Ribonuclease Protection Assay ◽  
Mrna Levels ◽  
Pdgf Signaling ◽  
Novel Strategy ◽  
Ribonuclease Protection

Parathyroid bone disease in humans is caused by chronic hyperparathyroidism (HPT). Continuous infusion of PTH into rats results in histological changes similar to parathyroid bone disease, including increased bone formation, focal bone resorption, and severe peritrabecular fibrosis, whereas pulsatile PTH increases bone formation without skeletal abnormalities. Using a cDNA microarray with over 5000 genes, we identified an association between increased platelet-derived growth factor-A (PDGF-A) signaling and PTH-induced bone disease in rats. Verification of PDGF-A overexpression was accomplished with a ribonuclease protection assay. Using immunohistochemistry, PDGF-A peptide was localized to mast cells in PTH-treated rats. We also report a novel strategy for prevention of parathyroid bone disease using triazolopyrimidine (trapidil). Trapidil, an inhibitor of PDGF signaling, did not have any effect on indexes of bone turnover in normal rats. However, dramatic reductions in marrow fibrosis and bone resorption, but not bone formation, were observed in PTH-treated rats given trapidil. Also, trapidil antagonized the PTH-induced increases in mRNA levels for PDGF-A. These results suggest that PDGF signaling is important for the detrimental skeletal effects of HPT, and drugs that target the cytokine or its receptor might be useful in reducing or preventing parathyroid bone disease.

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