The effect of oral dabigatran etexilate on bone density, strength, and microstructure in female and male mice

Abstract Objectives Glucocorticoid-induced osteoporosis (dexamethasone) is a primary cause of secondary osteoporosis by the decreasing formation and increasing resorption activities. Previously, the in vitro study showed that 70% ethanol and aqueous extract of deer antler have increased alkaline phosphatase in osteoblast cell that known as marker of bone formation. The mind of this study is to analyze the effect of deer antlers in increasing the bone trabecular density of osteoporosis-induced male mice. Methods This study used a post-test control group design. A total of 54 healthy male mice were randomly divided to nine groups, i.e., healthy control, osteoporotic, positive control, 70% ethanol (4, 8, and 12 mg/kg BW), and aqueous extracts (4, 8, and 12 mg/kg BW) of deer antler groups. All of the interventions were given 1 mL of test sample for 4 weeks orally. The bone densities were determined using histomorphometry by Image J and Adobe Photoshop. The statistical data were performed using SPSS 23 and statistical significance was set at p<0.05. Results The results showed that alendronate group, 70% ethanol, and aqueous extract groups increased bone density and calcium levels in serum (p<0.05) compared to osteoporotic group in dose dependent manner. It indicated that 70% ethanol and aqueous extract of deer antler stimulating bone turnover and aqueous extract showed the highest. Conclusions Dexamethasone induction for 4 weeks caused osteoporotic mice and the administration of 70% ethanol and aqueous extracts of deer antler from East Kalimantan increased trabecular bone density and calcium levels in dose dependent manner.

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The Effects of Hyperlipidemia on Implant Osseointegration in the Mouse Femur

Journal of Oral Implantology ◽

10.1563/aaid-joi-d-13-00105 ◽

2015 ◽

Vol 41 (2) ◽

pp. e7-e11 ◽

Cited By ~ 16

Author(s):

Armand Keuroghlian ◽

Ana Dilza Viana Barroso ◽

Gary Kirikian ◽

Olga Bezouglaia ◽

Yin Tintut ◽

...

Keyword(s):

Bone Density ◽

Titanium Implant ◽

Male Mice ◽

High Fat ◽

Lower Serum ◽

Beneficial Effects ◽

Cholesterol Levels ◽

Lower Serum Cholesterol ◽

Implant Therapy ◽

Bone Quantity

A high-fat (HF) diet inducing hyperlipidemia has been associated with the pathophysiology of major diseases, such as atherosclerosis and osteoporosis. A HF diet has significant adverse effects on bone, including lower bone density, volume, and strength. Statins, drugs that lower serum cholesterol levels have beneficial effects on bone metabolism. Since the host's bone quantity, quality, and healing potential play a crucial role in osseointegration of dental implants, we hypothesized that hyperlipidemia may negatively affect implant osseointegration. In the present study, we evaluated the effects of hyperlipidemia on implant osseointegration in mice. Atherosclerosis susceptible C57BL/6J male mice were randomly placed on a control chow or a HF diet. After 12 weeks on the diet, each mouse received a titanium implant in the proximal metaphysis of the femur. The animals were humanely killed at 4 or 8 weeks after the implant surgery. Results showed that the mice fed a HF diet had significantly increased implant loss as well as decreased formation and strength of bone-to-implant interface. These results support the hypothesis that a HF diet can significantly compromise osseointegration, causing poor outcome in dental implant therapy.

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Beneficial effects of Lactobacillus reuteri 6475 on bone density in male mice is dependent on lymphocytes

Scientific Reports ◽

10.1038/s41598-019-51293-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Fraser L. Collins ◽

Naiomy Deliz Rios-Arce ◽

Jonathan D. Schepper ◽

A. Daniel Jones ◽

Laura Schaefer ◽

...

Keyword(s):

T Cells ◽

Lymph Node ◽

Bone Density ◽

Mesenteric Lymph Node ◽

Lactobacillus Reuteri ◽

Male Mice ◽

Wild Type ◽

Beneficial Effects ◽

Secreted Factors ◽

Mesenteric Lymph

Abstract Oral treatment with probiotic bacteria has been shown to prevent bone loss in multiple models of osteoporosis. In previous studies we demonstrated that oral administration of Lactobacillus reuteri in healthy male mice increases bone density. The host and bacterial mechanisms of these effects however are not well understood. The objective of this study was to understand the role of lymphocytes in mediating the beneficial effects of L. reuteri on bone health in male mice. We administered L. reuteri in drinking water for 4 weeks to wild type or Rag knockout (lack mature T and B lymphocytes) male mice. While L. reuteri treatment increased bone density in wild type, no significant increases were seen in Rag knockout mice, suggesting that lymphocytes are critical for mediating the beneficial effects of L. reuteri on bone density. To understand the effect of L. reuteri on lymphocytes in the intestinal tissues, we isolated mesenteric lymph node (MLN) from naïve wild type mice. In ex vivo studies using whole mesenteric lymph node (MLN) as well as CD3+ T-cells, we demonstrate that live L. reuteri and its secreted factors have concentration-dependent effects on the expression of cytokines, including anti-inflammatory cytokine IL-10. Fractionation studies identified that the active component of L. reuteri is likely water soluble and small in size (<3 kDa) and its effects on lymphocytes are negatively regulated by a RIP2 inhibitor, suggesting a role for NOD signaling. Finally, we show that T-cells from MLNs treated with L. reuteri supernatants, secrete factors that enhance osterix (transcription factor involved in osteoblast differentiation) expression in MC3T3-E1 osteoblasts. Together, these data suggest that L. reuteri secreted factors regulate T-lymphocytes which play an important role in mediating the beneficial effects of L. reuteri on bone density.

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The effect of oral dabigatran etexilate on bone density, strength, and microstructure in healthy mice

Bone Reports ◽

10.1016/j.bonr.2017.12.001 ◽

2018 ◽

Vol 8 ◽

pp. 9-17 ◽

Cited By ~ 2

Author(s):

Mikkel Bo Brent ◽

Jesper Skovhus Thomsen ◽

Annemarie Brüel

Keyword(s):

Bone Density ◽

Dabigatran Etexilate

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Oral administration of melatonin increases plasma calcium and magnesium and improves bone metabolism in aged male mice

Melatonin Research ◽

10.32794/mr112500113 ◽

2021 ◽

Vol 4 (4) ◽

pp. 581-591

Author(s):

Junko Igarashi-Migitaka ◽

Yusuke Maruyama ◽

Azusa Seki ◽

Jun Hirayama ◽

Atsuko Kamijo-Ikemori ◽

...

Keyword(s):

Bone Density ◽

Oral Administration ◽

Intestinal Absorption ◽

Bone Strength ◽

Statistical Significance ◽

Inorganic Phosphorus ◽

Plasma Calcium ◽

Femoral Diaphysis ◽

Male Mice ◽

Femoral Bone

We previously reported that the oral administration of melatonin from 4 to 20 months to male mice improved femoral bone strength and bone density during the aging. Additionally, melatonin receptor, MT2, was immunologically detected in both osteoblasts and osteoclasts of the mouse femoral bone. Thus, melatonin can act on both osteoblasts and osteoclasts to maintain bone strength during the aging process. Here, we analyzed plasma calcium (Ca2+), magnesium (Mg2+), and inorganic phosphorus ([PO4]3-) in 20-month-old male mice with or without administration melatonin (15-20 mg/kg/day) in drinking water. We found that plasma Ca2+ and Mg2+ levels in melatonin-treated mice increased significantly as compared with control mice. In [PO4]3-, melatonin administration tended to increase its plasma level, but did not reach statistical significance. The potential association between these divalent ions and metabolism markers of femoral bone was also examined. In the femoral diaphysis, the plasma Ca2+ and Mg2+ concentrations were positively correlated with periosteal and endosteal circumference which were significantly associated with the Strength Strain Index. Therefore, melatonin treatment enlarged femoral diaphysis and enhanced bone strength by increasing mineral depositions. In addition, the plasma melatonin levels were significantly positive correlation with total bone density and critical thickness in the femoral diaphysis. Since we had not observed the primary trabecular bone and osteoclasts in 20-month-old mice previously, it is suggested that plasma Ca2+ and Mg2+ are not elevated due to bone resorption. The increased plasma Ca2+ and Mg2+ by melatonin may originate from the intestinal absorption of these ions since melatonin binds to the vitamin D3 receptor, its activation is known to promote the intestinal absorption of Ca2+.

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Raloxifen prevents bone loss in castrated male mice

Physiological Research ◽

10.33549/physiolres.931003 ◽

2007 ◽

pp. 443-448

Author(s):

PD Broulík ◽

K Broulíková

Keyword(s):

Bone Density ◽

Bone Loss ◽

Seminal Vesicles ◽

Male Mice ◽

Receptor Modulator ◽

Low Concentrations ◽

Highly Sensitive ◽

Skeletal Effects ◽

Bone Minerals ◽

Androgenic Effect

Raloxifen is a selective estrogen receptor modulator which prevents bone loss in ovariectomized female mice in a fashion similar to estrogens. Since testosterone-deficient male mice also lose bone mass, we were interested in testing the effects of raloxifen on bones in intact and castrated male mice. Bone density was significantly reduced in castrated animals (1.36+/-0.04 g/ml) as compared to intact animals (1.42+/-0.03 g/ml) (p<0.01). When castrated mice with extraordinarily low concentrations of testosterone and with reduced weight of seminal vesicles were treated with raloxifen, the changes in bone density and bone minerals resulting from castration (1.36+/-0.04 g/ml) were entirely prevented (1.40+/-0.01 g/ml). Cortical bone was lost in orchidectomized mice, and this decrease in cortical thickness of the femur was prevented by raloxifen administration. Raloxifen in a dose used in humans for treatment of osteoporosis decreased the weight of seminal vesicles, an organ which is highly sensitive to the androgenic effect, decreased the concentration of testosterone (12.5+/-2.8 micromol/l) (p<0.01) but not to the same level as in the case of castrated animals (0.6+/-0.3 micromol/l), and did not have any effect on bone density or mineral content in intact mice. The results of the present study may thus be interpreted as supporting the hypothesis that raloxifen is an effective agent against the deleterious effects of castration-induced osteopenia in male mice and also support the hypothesis that estrogens may have physiological skeletal effects in male mice.

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Prepubertal Di-n-Butyl Phthalate Exposure Alters Sertoli and Leydig Cell Function and Lowers Bone Density in Adult Male Mice

Endocrinology ◽

10.1210/en.2015-1936 ◽

2016 ◽

Vol 157 (7) ◽

pp. 2595-2603 ◽

Cited By ~ 10

Author(s):

Amanda Bielanowicz ◽

Rachelle W. Johnson ◽

Hoey Goh ◽

Sarah C. Moody ◽

Ingrid J. Poulton ◽

...

Keyword(s):

Bone Density ◽

Adult Male ◽

Leydig Cell ◽

Cell Function ◽

Male Mice ◽

Phthalate Exposure ◽

Butyl Phthalate ◽

Leydig Cell Function

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Ultrastructural Lesions Produced by Alcohol and Sucrose in the Heart and Liver of C57BL Mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100068035 ◽

1970 ◽

Vol 28 ◽

pp. 208-209

Author(s):

K.K. SEKHRI ◽

C.S. ALEXANDER ◽

H.T. NAGASAWA

Keyword(s):

Osmium Tetroxide ◽

Male Mice ◽

Alcohol Group ◽

Group Iii ◽

Group I ◽

C57bl Mice ◽

Group Ii

C57BL male mice (Jackson Lab., Bar Harbor, Maine) weighing about 18 gms were randomly divided into three groups: group I was fed sweetened liquid alcohol diet (modified Schenkl) in which 36% of the calories were derived from alcohol; group II was maintained on a similar diet but alcohol was isocalorically substituted by sucrose; group III was fed regular mouse chow ad lib for five months. Liver and heart tissues were fixed in 2.5% cacodylate buffered glutaraldehyde, post-fixed in 2% osmium tetroxide and embedded in Epon-araldite.

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