scholarly journals Rhus javanicaGall Extract Inhibits the Differentiation of Bone Marrow-Derived Osteoclasts and Ovariectomy-Induced Bone Loss

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Tae-Ho Kim ◽  
Eui Kyun Park ◽  
Man-Il Huh ◽  
Hong Kyun Kim ◽  
Shin-Yoon Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Loss ◽  
Bone Turnover ◽  
Bone Remodeling ◽  
Bone Mineral ◽  
Osteoclast Differentiation ◽  
Protective Effects ◽  
Mineral Density ◽  
Femoral Bone Mineral Density

Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects ofRhus javanica(R. javanica) extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts ofR. javanica(eGr) cocoons spun byRhus javanica(Bell.) Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr) or 100% ethanolic extract (eeGr) on ovariectomy- (OVX-) induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT) was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks) augmented the inhibition of femoral bone mineral density (BMD), bone mineral content (BMC), and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss.

scholarly journals Icariin Prevents Diabetes-Induced Bone Loss in Rats by Reducing Blood Glucose and Suppressing Bone Turnover

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1871 ◽  
Author(s):  
Shanshan Qi ◽  
Jia He ◽  
Hongxing Zheng ◽  
Chen Chen ◽  
Shiqiang Lan
Keyword(s):  
Bone Mineral Density ◽  
Bone Marrow ◽  
Blood Glucose ◽  
Bone Loss ◽  
Bone Turnover ◽  
Bone Histomorphometry ◽  
Diabetic Rats ◽  
Protective Effects ◽  
Mineral Density ◽  
Diabetic Osteoporosis

Diabetic Osteoporosis (DOP) is a common metabolic bone disease, characterized by decreased bone mineral density (BMD) and destruction of bone microstructure. It has been reported that icariin is beneficial for estrogen deficiency-induced osteoporosis, and alcohol-induced osteoporosis; whether icariin has protective effects on diabetes-induced osteoporosis has not been reported. In this study, a rat model of diabetic osteoporosis was established by streptozotocin injection, the bone protective effects and potential mechanism of icariin on diabetes-induced bone loss was observed. Thirty 8-week-old female Sprague Dawley rats were divided into control group (vehicle treatment), T1DM (diabetic) group and T1DM-icariin (ICA) group (diabetic rats treated with icariin), 10 rats in each group. The bone histomorphometry parameters, bone mineral density (BMD), serum bone turnover markers, and bone marrow adipogenesis were analyzed after 8 weeks of icariin administration. The results showed consumption of icariin at a doses of 100 mg kg−1 decreased blood glucose, and increased the BMD of diabetic rats. Icariin effectively decreased serum bone turnover marker levels, including CTX-1, ALP, TRACP 5b, osteocalcin, and PINP. Meanwhile, the bone histomorphometry parameters, the number of osteoclasts per bone perimeter were turned to be normal level, and the icariin treatment suppressed bone marrow adipogenesis. The runt-related transcription factor 2 (RUNX 2), as well as the osteoprotegerin (OPG)/receptor activator of nuclear factor-κ B ligand (RANKL) ratio in serum and bone tissues were increased significantly after icariin treatment in diabetic rats. All of the above indicate that oral administration of icariin can prevent diabetic osteoporosis; the effect is mainly related to its ability to reduce blood glucose, inhibit bone turnover and bone marrow adipogenesis, as well as up-regulate bone RUNX 2, and OPG expression.

scholarly journals Ethanolic Extract of Rubus coreanus Fruits Inhibits Bone Marrow-Derived Osteoclast Differentiation and Lipopolysaccharide-Induced Bone Loss

2017 ◽  
Vol 12 (12) ◽  
pp. 1934578X1701201
Author(s):  
Tae-Ho Kim ◽  
Chae Gyeong Jeong ◽  
Hyeong-U Son ◽  
Man-Il Huh ◽  
Shin-Yoon Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Ethanolic Extract ◽  
Type I ◽  
Mineral Density ◽  
Induced Differentiation ◽  
Rubus Coreanus

The inhibition of osteoclast differentiation/bone resorption is a well-known therapeutic strategy for controlling pathological and postmenopausal bone loss. Natural products that specifically inhibit osteoclastogenesis could therefore be developed as antiresorptive drugs for the treatment of metabolic bone disorders characterized by excessive osteoclastic bone resorption. We therefore examined the effects of Rubus coreanus extract (eeRc) on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced differentiation of bone marrow macrophages (BMMs) into osteoclasts and pit formation in vitro. Additionally, the in vivo effects of the eeRc were observed in mice with lipopolysaccharide (LPS)-induced bone erosion. In this study, we found that the ethanolic extract of Rubus coreanus fruits considerably suppressed the RANKL-induced differentiation of primary BMMs into osteoclasts and bone-resorbing activity of mature osteoclasts. Oral administration of eeRc attenuated LPS-induced bone loss in vivo, as demonstrated by the reversal of LPS-induced reduction in bone volume per tissue volume, bone mineral density, and trabecular number to some extent in eeRc-treated mice. In addition, eeRc slightly decreased the serum levels of C-terminal telopeptide fragments of type I collagen, the collagen-breakdown product generated by osteoclasts. Collectively, our results indicate that eeRc has the potential to inhibit bone loss by blocking osteoclast differentiation and could therefore be a promising natural product for the prevention and/or treatment of inflammatory bone loss.

scholarly journals Increased PTHrP and Decreased Estrogens Alter Bone Turnover but Do Not Reproduce the Full Effects of Lactation on the Skeleton

Endocrinology ◽  
2010 ◽  
Vol 151 (12) ◽  
pp. 5591-5601 ◽  
Author(s):  
Laleh Ardeshirpour ◽  
Susan Brian ◽  
Pamela Dann ◽  
Joshua VanHouten ◽  
John Wysolmerski
Keyword(s):  
Bone Mineral Density ◽  
Bone Resorption ◽  
Bone Loss ◽  
Bone Turnover ◽  
Bone Mineral ◽  
Gnrh Agonist ◽  
Estrogen Deficiency ◽  
Trabecular Architecture ◽  
Mineral Density ◽  
Long Acting

During lactation, calcium is mobilized from the maternal skeleton to supply the breast for milk production. This results in rapid but fully reversible bone loss. Prior studies have suggested that PTHrP, secreted from the breast, and estrogen deficiency, due to suckling-induced central hypogonadism, combine to trigger bone resorption. To determine whether this combination was sufficient to explain bone loss during lactation, we raised PTHrP levels and decreased levels of estrogens in nulliparous mice. PTHrP was infused via osmotic minipumps and estrogens were decreased either by using leuprolide, a long-acting GnRH agonist, or by surgical ovariectomy (OVX). Bone mineral density declined by 23.2 ± 1.3% in the spine and 16.8 ± 1.9% in the femur over 10 d of lactation. This was accompanied by changes in trabecular architecture and an increase in both osteoblast and osteoclast numbers. OVX and PTHrP infusion both induced a modest decline in bone mineral density over 10 d, but leuprolide treatment did not. The combination of OVX and PTHrP was more effective than either treatment alone, but there was no interaction between PTHrP and leuprolide. None of the treatments reproduced the same degree of bone loss caused by lactation. However, both forms of estrogen deficiency led to an increase in osteoclasts, whereas infusion of PTHrP increased both osteoblasts and osteoclasts. Therefore, although the combination of PTHrP and estrogen deficiency contributes to bone loss, it is insufficient to reproduce the full response of the skeleton to lactation, suggesting that other factors also regulate bone metabolism during this period.

Impaired Estrogen Sensitivity in Bone by Inhibiting Both Estrogen Receptor a and b Pathways*

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Bone Mineral Density ◽  
Estrogen Receptor ◽  
Bone Loss ◽  
Bone Turnover ◽  
Bone Mineral ◽  
Female Rats ◽  
Wild Type ◽  
Mineral Density ◽  
Transgenic Rats ◽  
Estrogen Sensitivity

Although it is well established that estrogen deficiencycauses osteoporosis among the postmenopausalwomen, the involvement of estrogen receptor (ER) in itspathogenesis still remains uncertain. In the presentstudy, we have generated rats harboring a dominantnegative ERa, which inhibits the actions of not only ERabut also recently identified ERb. Contrary to our expectation,the bone mineral density (BMD) of the resultingtransgenic female rats was maintained at the same levelwith that of the wild-type littermates when sham-operated.In addition, ovariectomy-induced bone loss wasobserved almost equally in both groups. Strikingly, however,the BMD of the transgenic female rats, after ovariectomized,remained decreased even if 17b-estradiol(E2) was administrated, whereas, in contrast, the decreaseof littermate BMD was completely prevented byE2. Moreover, bone histomorphometrical analysis ofovariectomized transgenic rats revealed that the higherrates of bone turnover still remained after treatmentwith E2. These results demonstrate that the preventionfrom the ovariectomy-induced bone loss by estrogen ismediated by ER pathways and that the maintenanceof BMD before ovariectomy might be compensatedby other mechanisms distinct from ERa and ERbpathways.

scholarly journals Nox2 Activity Is Required in Obesity-Mediated Alteration of Bone Remodeling

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Md Mizanur Rahman ◽  
Amina El Jamali ◽  
Ganesh V. Halade ◽  
Allal Ouhtit ◽  
Haissam Abou-Saleh ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Marrow ◽  
Bone Remodeling ◽  
Bone Mineral ◽  
Bone Marrow Cells ◽  
Bone Marrow Microenvironment ◽  
Ros Generation ◽  
Chow Diet ◽  
Mineral Density ◽  
Marrow Cells

Despite increasing evidence suggesting a role for NADPH oxidases (Nox) in bone pathophysiology, whether Nox enzymes contribute to obesity-mediated bone remodeling remains to be clearly elucidated. Nox2 is one of the predominant Nox enzymes expressed in the bone marrow microenvironment and is a major source of ROS generation during inflammatory processes. It is also well recognized that a high-fat diet (HFD) induces obesity, which negatively impacts bone remodeling. In this work, we investigated the effect of Nox2 loss of function on obesity-mediated alteration of bone remodeling using wild-type (WT) and Nox2-knockout (KO) mice fed with a standard lab chow diet (SD) as a control or a HFD as an obesity model. Bone mineral density (BMD) of mice was assessed at the beginning and after 3 months of feeding with SD or HFD. Our results show that HFD increased bone mineral density to a greater extent in KO mice than in WT mice without affecting the total body weight and fat mass. HFD also significantly increased the number of adipocytes in the bone marrow microenvironment of WT mice as compared to KO mice. The bone levels of proinflammatory cytokines and proosteoclastogenic factors were also significantly elevated in WT-HFD mice as compared to KO-HFD mice. Furthermore, the in vitro differentiation of bone marrow cells into osteoclasts was significantly increased when using bone marrow cells from WT-HFD mice as compared to KO-HFD mice. Our data collectively suggest that Nox2 is implicated in HFD-induced deleterious bone remodeling by enhancing bone marrow adipogenesis and osteoclastogenesis.

scholarly journals Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism

2018 ◽  
Vol 4 (4) ◽  
pp. 37 ◽  
Author(s):  
Giuseppina E. Grieco ◽  
Dorica Cataldo ◽  
Elena Ceccarelli ◽  
Laura Nigi ◽  
Giovanna Catalano ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Type 1 Diabetes ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Bone Remodeling ◽  
Bone Mineral ◽  
Bone Fragility ◽  
Bone Homeostasis ◽  
Mineral Density

Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an early detection of such alterations and to envisage appropriate therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs which negatively regulate genes expression. Of note, miRNAs can be secreted in biological fluids through their association with different cellular components and, in such context, they may represent both candidate biomarkers and/or mediators of bone metabolism alterations. Here, we aimed at identifying miRNAs differentially expressed in serum of T1D patients and potentially involved in bone loss in type 1 diabetes. We selected six miRNAs previously associated with T1D and bone metabolism: miR-21; miR-24; miR-27a; miR-148a; miR-214; and miR-375. Selected miRNAs were analyzed in sera of 15 T1D patients (age: 33.57 ± 8.17; BMI: 21.4 ± 1.65) and 14 non-diabetic subjects (age: 31.7 ± 8.2; BMI: 24.6 ± 4.34). Calcium, osteocalcin, parathormone (PTH), bone ALkaline Phoshatase (bALP), and Vitamin D (VitD) as well as main parameters of bone health were measured in each patient. We observed an increased expression of miR-148a (p = 0.012) and miR-21-5p (p = 0.034) in sera of T1D patients vs non-diabetic subjects. The correlation analysis between miRNAs expression and the main parameters of bone metabolism, showed a correlation between miR-148a and Bone Mineral Density (BMD) total body (TB) values (p = 0.042) and PTH circulating levels (p = 0.033) and the association of miR-21-5p to Bone Mineral Content-Femur (BMC-FEM). Finally, miR-148a and miR-21-5p target genes prediction analysis revealed several factors involved in bone development and remodeling, such as MAFB, WNT1, TGFB2, STAT3, or PDCD4, and the co-modulation of common pathways involved in bone homeostasis thus potentially assigning a role to both miR-148a and miR-21-5p in bone metabolism alterations. In conclusion, these results lead us to hypothesize a potential role for miR-148a and miR-21-5p in bone remodeling, thus representing potential biomarkers of bone fragility in T1D.

scholarly journals Insight into Bone Protective Mechanisms of Dried Plum Using an Ovariectomized Rat Model (OR18-06-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Bahram Arjmandi ◽  
Neda Akhavan ◽  
Joseph Munoz ◽  
Kelli George ◽  
Elizabeth Foley ◽  
...  
Keyword(s):  
Bone Loss ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Rat Model ◽  
Bone Histomorphometry ◽  
Hormone Deficiency ◽  
Ovarian Hormone ◽  
Protective Effects ◽  
Mineral Density ◽  
Funding Sources

Abstract Objectives Osteoporosis may result in fracture with dire consequences. For instance, 40% of people with their second hip fracture die within two years. Aside from pharmaceutical interventions, that are not free of side effects, identifying edible and safe foods to prevent bone loss is of importance. We and others have shown that dried plum (DP) prevents loss of bone both in ovariectomized (Ovx) rat models as well as postmenopausal women. Hence, the purpose of this study was to examine the bone protective mechanism of action of DP, a rich source of phenolic and flavonoid compounds, in preventing bone loss using a rat model of ovarian hormone deficiency. Methods Forty-eight 90-day old female Sprague-Dawley rats were divided into four groups: sham-operated (Sham), Ovx, Ovx + 5% DP (low-dose, LD), and Ovx + 25% DP (high-dose, HD). Treatments started immediately after surgery and continued for 45 days. Animals were either fed a semi-purified diet, or a similar diet in which 5% or 25% of the diet (w/w) consisted of DP. All diets were made isocaloric and isonitrogenous containing 0.4% calcium and 0.3% phosphorus. Food intake, bone mineral density, bone mineral content, body/organ weight, blood biomarkers of bone metabolism, and static bone histomorphometry were assessed. Results The right femoral and the 4th lumbar vertebrae density were significantly (P < 0.05) lower in the Ovx control rats compared to Sham. The loss of density in both bones were completely prevented by HD-DP (P < 0.05). The HD-DP increased insulin-like growth factor-1 (IGF-1) significantly (P < 0.05) from 110 ± 4 ηmol/L to 135 ± 4 ηmol/L. In terms of bone histomorphometry, % bone area was significantly (P < 0.05) decreased as a result of Ovx and HD-DP nearly prevented this decrease (P > 0.05). Although the endosteal perimeter (mm2) was not statistically different from other groups, the endosteal perimeter of the HD-DP group was 13.6% lower than that of the Ovx group. Conclusions The bone protective effects of DP may, in part, be explained by an increase in IGF-1, which is strongly correlated with bone formation, and a decrease in the endosteal perimeter, which is increased in ovarian hormone deficiency and postmenopausal women. Future studies should examine radiolabeling compounds in DP to see how they contribute to its bone protective effects. Funding Sources There have been no funding sources.

scholarly journals Effects of high-protein intake on bone turnover in long-term bed rest in women

2017 ◽  
Vol 42 (5) ◽  
pp. 537-546 ◽  
Author(s):  
Martina Heer ◽  
Natalie Baecker ◽  
Petra Frings-Meuthen ◽  
Sonja Graf ◽  
Sara R. Zwart ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Turnover ◽  
Muscle Mass ◽  
Protein Intake ◽  
Bed Rest ◽  
High Protein ◽  
Mineral Density ◽  
High Protein Intake ◽  
Potassium Intake

Bed rest (BR) causes bone loss, even in otherwise healthy subjects. Several studies suggest that ambulatory subjects may benefit from high-protein intake to stimulate protein synthesis and to maintain muscle mass. However, increasing protein intake above the recommended daily intake without adequate calcium and potassium intake may increase bone resorption. We hypothesized that a regimen of high-protein intake (HiPROT), applied in an isocaloric manner during BR, with calcium and potassium intake meeting recommended values, would prevent any effect of BR on bone turnover. After a 20-day ambulatory adaptation to a controlled environment, 16 women participated in a 60-day, 6° head-down-tilt (HDT) BR and were assigned randomly to 1 of 2 groups. Control (CON) subjects (n = 8) received 1 g/(kg body mass·day)−1 dietary protein. HiPROT subjects (n = 8) received 1.45 g protein/(kg body mass·day)−1 plus an additional 0.72 g branched-chain amino acids per day during BR. All subjects received an individually tailored diet (before HDTBR: 1888 ± 98 kcal/day; during HDTBR: 1604 ± 125 kcal/day; after HDTBR: 1900 ± 262 kcal/day), with the CON group’s diet being higher in fat and carbohydrate intake. High-protein intake exacerbated the BR-induced increase in bone resorption marker C-telopeptide (>30%) (p < 0.001) by the end of BR. Bone formation markers were unaffected by BR and high-protein intake. We conclude that high-protein intake in BR might increase bone loss. Further long-duration studies are mandatory to show how the positive effect of protein on muscle mass can be maintained without the risk of reducing bone mineral density.

scholarly journals Crif1 Promotes Osteoporosis in Mice after Radiation

2019 ◽  
Author(s):  
Lixin Xiang ◽  
Li Chen ◽  
Yang Xiang ◽  
Fengjie Li ◽  
Xiaomei Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Loss ◽  
Bone Marrow Cells ◽  
Current Knowledge ◽  
Osteoclast Differentiation ◽  
Protein Docking ◽  
Rankl Expression ◽  
Marrow Cells

AbstractRadiation induces rapid bone loss and enhances bone resorption and RANKL expression. RANKL provides the crucial signal to induce osteoclast differentiation and plays an important role in bone resorption. However, the mechanisms of radiation-induced osteoporosis are not fully understood. Here, we show that Crif1 expression increases in bone marrow cells after radiation. Conditional Crif1 deletion in bone marrow cells causes decreases in RANKL expression and the RANKL/OPG ratio, and relieves bone loss after radiation in mice. We further demonstrated in vitro that Crif1 promotes RANKL secretion via the cAMP/PKA pathway. Moreover, protein-protein docking screening identified five compounds as Crif1 inhibitors; these compounds dramatically suppressed RANKL secretion and CREB phosphorylation when cells were exposed to forskolin. This study enriches current knowledge of the pathogenesis of osteoporosis and provides insights into potential therapeutic strategies for osteoporosis treatment.

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