scholarly journals Green Tomato Extract Prevents Bone Loss in Ovariectomized Rats, a Model of Osteoporosis

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3210
Author(s):  
Farida S. Nirmala ◽  
Hyunjung Lee ◽  
Ji-Sun Kim ◽  
Taeyoul Ha ◽  
Chang Hwa Jung ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Postmenopausal Osteoporosis ◽  
Ovariectomized Rats ◽  
Bone Homeostasis ◽  
Sprague Dawley ◽  
Micro Computed Tomography ◽  
Tomato Extract ◽  
Ovx Rats

Although drug therapies are available for postmenopausal osteoporosis, these drugs are not free of side effects and long-term adherence to them are low. A safe and effective nutritional approach to counter postmenopausal osteoporosis is an important research goal. We fed ovariectomized (OVX) Sprague–Dawley rats a diet supplemented with 1% or 2% green tomato extract (GTE). After 12 weeks, micro-computed tomography scans revealed that GTE supplementation effectively prevented distal femur bone loss. This prevention was due to improved bone formation and suppressed bone resorption as observed by the regulation of osteoblast and osteoclast activities. GTE supplementation also improved bone formation through Bmp2-Smad 1/5/8-Runx2 signaling, while bone resorption was regulated by the receptor activator of nuclear factor kappa-B (RANKL)/osteoprogeterin (OPG) pathway. These results suggest that GTE supplementation prevents severe postmenopausal bone loss by maintaining the regulation of bone homeostasis in OVX rats. GTE as a diet supplement might be a potential novel alternative for the prevention of postmenopausal osteoporosis.

scholarly journals Treatment withRhizoma DioscoreaeExtract Has Protective Effect on Osteopenia in Ovariectomized Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Zhiguo Zhang ◽  
Lihua Xiang ◽  
Dong Bai ◽  
Xiaowei Fu ◽  
Wenlai Wang ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Pathway Analysis ◽  
Ovariectomized Rats ◽  
Inhibitory Effects ◽  
Ovx Rats ◽  
Rank Signaling

The aims of this study were to evaluate the osteoprotective effect of aqueous extract fromRhizoma Dioscoreae(RDE) on rats with ovariectomy- (OVX-) induced osteopenia. Our results show that RDE could inhibit bone loss of OVX rats after a 12-week treatment. The microarray analysis showed that 68 genes were upregulated and that 100 genes were downregulated in femurs of the RDE group rats compared to those in the OVX group. The Ingenuity Pathway Analysis (IPA) showed that several downregulated genes had the potential to code for proteins that were involved in the Wnt/β-catenin signaling pathway (Sost, Lrp6, Tcf7l2, and Alpl) and the RANKL/RANK signaling pathway (Map2k6 and Nfatc4). These results revealed that the mechanism for an antiosteopenic effect of RDE might lie in the synchronous inhibitory effects on both the bone formation and the bone resorption, which is associated with modulating the Wnt/β-catenin signaling and the RANKL/RANK signaling.

scholarly journals Novel Osteogenic Factors derived from Functional Food: Role in Prevention of Osteoporosis

2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Masayoshi Yamaguchi
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Functional Food ◽  
Human Subjects ◽  
Osteoclastic Bone Resorption ◽  
Bone Homeostasis ◽  
Osteoblastic Bone Formation ◽  
Prevention Of Osteoporosis ◽  
Osteogenic Effect

<p>Bone homeostasis is maintained through a delicate balance between osteoblastic bone formation and osteoclastic bone resorption. Bone loss is caused by decreasing in osteoblastic bone formation and increase in osteoclastic bone resorption, thereby leading to osteoporosis. Functional food factors may play a role in<br />the prevention of osteoporosis. Functional food factors including genistein, menaquinone-7 (vitamin K2) and β-cryptoxanthine have been shown to possess a potential osteogenic effect. These factors have been shown to reveal stimulatory effects on osteoblastic bone formation and suppressive effects on osteoclastic<br />bone resorption. Dietary intake of these factors has been shown to reveal preventive effects on bone loss in animal models of osteoporosis and human subjects. This review will introduce our findings concerning roles of functional food factors in regulation of bone homeostasis and prevention of osteoporosis.</p>

scholarly journals Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice

2018 ◽  
Vol 238 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Thomas Funck-Brentano ◽  
Karin H Nilsson ◽  
Robert Brommage ◽  
Petra Henning ◽  
Ulf H Lerner ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Cortical Bone ◽  
Bone Strength ◽  
Bending Test ◽  
Bone Homeostasis ◽  
Mineral Density

WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, µCT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.

scholarly journals New Bone Formation with Teriparatide [Human Parathyroid Hormone-(1–34)] Is Not Retarded by Long-Term Pretreatment with Alendronate, Estrogen, or Raloxifene in Ovariectomized Rats

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 2008-2015 ◽  
Author(s):  
Yanfei L. Ma ◽  
Henry U. Bryant ◽  
Qingqiang Zeng ◽  
Allen Schmidt ◽  
Jennifer Hoover ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Formation Rate ◽  
Prior Exposure ◽  
Ovariectomized Rats ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Teriparatide Treatment ◽  
Antiresorptive Agents ◽  
Ovx Rats

With the ready availability of several osteoporosis therapies, teriparatide [human PTH-(1–34)] is likely to be prescribed to postmenopausal women with prior exposure to agents that prevent bone loss, such as bisphosphonates, estrogen, or selective estrogen receptor modulators. Therefore, we evaluated the ability of once daily teriparatide to induce bone formation in ovariectomized (Ovx) rats with extended prior exposure to various antiresorptive agents, such as alendronate (ABP), 17α-ethinyl estradiol (EE), or raloxifene (Ral). Sprague Dawley rats were Ovx and treated with ABP (28 μg/kg, twice weekly), EE (0.1 mg/kg·d), or Ral (1 mg/kg·d) for 10 months before switching to teriparatide 30 μg/kg·d for another 2 months. Analysis of the proximal tibial metaphysis showed that all three antiresorptive agents prevented ovariectomy-induced bone loss after 10 months, but were mechanistically distinct, as shown by histomorphometry. Before teriparatide treatment, ABP strongly suppressed activation frequency and bone formation rate to below levels in other treatment groups, whereas these parameters were not different from sham values for EE or Ral. Trabecular area for ABP, EE, and Ral were greater than that in Ovx controls. However, the trabecular bone effects of ABP were attributed not only to effects on the secondary spongiosa, but also to the preservation of primary spongiosa, which was prevented from remodeling. After 2 months of teriparatide treatment, lumbar vertebra showed relative bone mineral density increases of 18%, 7%, 11%, and 10% for vehicle/teriparatide, ABP/teriparatide, EE/teriparatide, and Ral/teriparatide, respectively, compared with 10 month levels. Histomorphometry showed that trabecular area was increased by 105%, 113%, 36%, and 48% for vehicle/teriparatide, ABP/teriparatide, EE/teriparatide, and Ral/teriparatide, respectively, compared with 10 month levels. Teriparatide enhanced mineralizing surface, mineral apposition rate, and bone formation rate in all groups. Compression testing of vertebra showed that teriparatide improved strength (peak load) and toughness in all groups to a proportionately similar extent compared with 10 month levels. These data showed a surprising ability of the rat skeleton to respond to teriparatide despite extensive pretreatment with ABP, EE, or Ral. Therefore, the mature skeleton of Ovx rats remains highly responsive to the appositional effects of teriparatide regardless of pretreatment status in terms of cancellous bone area or rate of bone turnover.

Long-Term Therapy with a New Chemically Modified Tetracycline (CMT-8) Inhibits Bone Loss in Femurs of Ovariectomized Rats

1998 ◽  
Vol 12 (1) ◽  
pp. 76-81 ◽  
Author(s):  
T. Sasaki ◽  
N.S. Ramamurthy ◽  
L.M. Golub
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Trabecular Bone ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Term Therapy ◽  
Ovx Rats ◽  
Trabecular Bone Loss ◽  
Bone Trabeculae

The effect of a new non-antimicrobial analog of tetracycline (CMT-8) on bone loss in ovariectomized (OVX) rats was examined. Three-month-old female rats were ovariectomized, and one week later, were distributed into 3 groups: sham-operated non-OVX controls, vehicle-treated OVX controls, and CMT-8-treated OVX rats. After 145 days of daily CMT-8 administration, the intact femurs were dissected and examined by several histological and histomorphometric techniques. OVX significantly (p < 0.01) decreased trabecular bone volume by 53.4% in the metaphyses compared with sham-operated controls. CMT-8 therapy produced a significant (p < 0.05) inhibition of trabecular bone loss and also induced bone formation in the OVX rats. Of interest, the newly synthesized bone in the CMT-treated OVX rats was found to increase the "connectivity" of the trabecular "struts" by bridging the adjacent longitudinal bone trabeculae, forming dense, platelike bone trabeculae. These results strongly suggest that long-term CMT-8 therapy effectively inhibits bone loss after OVX, not only by inhibiting bone resorption but also by inducing new bone formation in the trabecular areas of long bones.

Chronic treatment with angiotensin AT1 receptor antagonists reduced serum but not bone TGF-β1 levels in ovariectomized rats

2009 ◽  
Vol 87 (1) ◽  
pp. 51-55 ◽  
Author(s):  
Yong-Qi Li ◽  
Hui Ji ◽  
Yang Shen ◽  
Li-Ju Ding ◽  
Pei Zhuang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Postmenopausal Osteoporosis ◽  
Chronic Treatment ◽  
Transforming Growth Factor ◽  
Ovariectomized Rats ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mineral Density ◽  
Receptor Antagonists ◽  
Ovx Rats ◽  
At1 Receptor Antagonists

Approximately 50% of hypertensive patients are postmenopausal women; therefore, any antihypertensive therapy must not adversely affect bone loss in this population. Recently, however, concern has been raised that use of angiotensin AT1 receptor antagonists may increase the tendency to develop postmenopausal osteoporosis by decreasing transforming growth factor-β1 (TGF-β1), which has been implicated in bone mass maintenance. In the present study, we selected telmisartan and valsartan as representatives of angiotensin AT1 receptor antagonists and used ovariectomized (OVX) rats as a model of human postmenopausal osteoporosis. After 3 months treatment with telmisartan (5 mg/kg daily) or valsartan (10 mg/kg daily), OVX rats showed no signs of adverse effects on bone mineral density of the lumbar vertebrae (L1–L5) or the total femur, nor did treatment affect serum levels of osteocalcin and osteoclast-derived tartrate-resistant acid phosphatase (TRACP-5b). Bone TGF-β1 content remained unchanged, although treatment with telmisartan and valsartan significantly reduced serum TGF-β1 levels (p < 0.05). In conclusion, chronic treatment with angiotensin AT1 receptor antagonists reduced serum but not bone TGF-β1 levels and did not accelerate ovariectomy-induced bone loss in rats.

5 alpha-Dihydrotestosterone partially restores cancellous bone volume in osteopenic ovariectomized rats

1994 ◽  
Vol 267 (6) ◽  
pp. E853-E859 ◽  
Author(s):  
J. H. Tobias ◽  
A. Gallagher ◽  
T. J. Chambers
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Bone Growth ◽  
Bone Volume ◽  
Ovariectomized Rats ◽  
Trabecular Thickness ◽  
Longitudinal Bone Growth ◽  
Periosteal Bone Formation

Although androgens are thought to be important for skeletal maintenance in females and males, little is known about the mechanisms involved. To investigate this question further, we examined the effects of administering 0.01, 0.1, or 1.0 mg/kg 5 alpha-dihydrotestosterone (DHT) for 60 days on the skeleton of ovariectomized rats. Treatment was delayed until 90 days after ovariectomy to enable bone loss to stabilize. We found that ovariectomy markedly reduced cancellous bone volume of the proximal tibial metaphysis due to a combination of loss and thinning of trabeculae. Cancellous bone volume was partially restored by all doses of DHT, with trabecular thickness, but not number, returning to that of sham-operated animals. DHT also stimulated longitudinal bone growth and endosteal and periosteal bone formation and suppressed histomorphometric indexes of cancellous bone resorption. This suggests that DHT influences skeletal metabolism in osteopenic ovariectomized rats both by stimulating bone formation and suppressing resorption, although it is unclear which, if any, of these actions predominate at cancellous sites.

scholarly journals Rhizoma drynariae total flavonoids combined with calcium carbonate ameliorates bone loss in experimentally induced Osteoporosis in rats via the regulation of Wnt3a/β-catenin pathway

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yimei Hu ◽  
Panyun Mu ◽  
Xu Ma ◽  
Jingru Shi ◽  
Zhendong Zhong ◽  
...  
Keyword(s):  
Calcium Carbonate ◽  
Bone Loss ◽  
Bone Formation ◽  
Chinese Herb ◽  
Estrogen Deficiency ◽  
Ovariectomized Rats ◽  
Cartilage Tissue ◽  
Total Flavonoids ◽  
Ovx Rats ◽  
Rhizoma Drynariae

Abstract Background Rhizoma drynariae, a traditional Chinese herb, is commonly used in treatment of bone healing in osteoporotic fractures. However, whether the Rhizoma drynariae total flavonoids (RDTF) can promote the absorption of calcium and enhance the bone formation is unclear. The aim of the present study was to investigate the preventive effects of RDTF combined with calcium carbonate (CaCO3) on estrogen deficiency-induced bone loss. Methods Three-month-old Sprague–Dawley rats were ovariectomized (OVX) and then treated with CaCO3, RDTF, and their admixtures for ten weeks, respectively. The bone trabecular microstructure, bone histopathological examination, and serum biomarkers of bone formation and resorption were determined in the rat femur tissue. The contents of osteoprotegerin (OPG), receptor activator of the NF-κB (RANK), and its ligand (RANKL) in marrow were analyzed by ELISA, and the protein expressions of Wnt3a, β-catenin, and phosphorylated β-catenin (p-β-catenin) were analyzed by Western blot. Statistical analysis was conducted by using one-way analysis of variance (ANOVA) followed by LSD post hoc analysis or independent samples t test using the scientific statistic software SPSS version 20.0 Results RDTF combined with CaCO3 could promote osteosis and ameliorate bone loss to improve the repair of cracked bone trabeculae of OVX rats. Furthermore, RDTF combined with CaCO3 also could prevent OVX-induced decrease in collagen fibers in the femoral tissue of ovariectomized rats and promote the regeneration of new bone or cartilage tissue, while CaCO3 supplementation promoted the increase in bone mineral content. Nevertheless, there was no difference in the expression of Wnt3a, β-catenin and p-β-catenin between osteopenic rats and RDTF treated rats, but RDTF combined with CaCO3 could activate the Wnt3a/β-catenin pathway. Conclusions RDTF combined with CaCO3 could ameliorate estrogen deficiency-induced bone loss via the regulation of Wnt3a/β-catenin pathway.

scholarly journals Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorption

2010 ◽  
Vol 207 (3) ◽  
pp. 257-263 ◽  
Author(s):  
Kotaro Azuma ◽  
Stephanie C Casey ◽  
Masako Ito ◽  
Tomohiko Urano ◽  
Kuniko Horie ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Volume Fraction ◽  
Pregnane X Receptor ◽  
Bending Test ◽  
Bone Homeostasis ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Trabecular Bones

The steroid and xenobiotic receptor (SXR) and its murine ortholog pregnane X receptor (PXR) are nuclear receptors that are expressed mainly in the liver and intestine where they function as xenobiotic sensors. In addition to its role as a xenobiotic sensor, previous studies in our laboratories and elsewhere have identified a role for SXR/PXR as a mediator of bone homeostasis. Here, we report that systemic deletion of PXR results in marked osteopenia with mechanical fragility in female mice as young as 4 months old. Bone mineral density (BMD) of PXR knockout (PXRKO) mice was significantly decreased compared with the BMD of wild-type (WT) mice. Micro-computed tomography analysis of femoral trabecular bones revealed that the three-dimensional bone volume fraction of PXRKO mice was markedly reduced compared with that of WT mice. Histomorphometrical analysis of the trabecular bones in the proximal tibia showed a remarkable reduction in bone mass in PXRKO mice. As for bone turnover of the trabecular bones, bone formation is reduced, whereas bone resorption is enhanced in PXRKO mice. Histomorphometrical analysis of femoral cortical bones revealed a larger cortical area in WT mice than that in PXRKO mice. WT mice had a thicker cortical width than PXRKO mice. Three-point bending test revealed that these morphological phenotypes actually caused mechanical fragility. Lastly, serum levels of phosphate, calcium, and alkaline phosphatase were unchanged in PXRKO mice compared with WT. Consistent with our previous results, we conclude that SXR/PXR promotes bone formation and suppresses bone resorption thus cementing a role for SXR/PXR as a key regulator of bone homeostasis.

scholarly journals A Novel Peptide, CK2.3, Improved Bone Formation in Ovariectomized Sprague Dawley Rats

2020 ◽  
Vol 21 (14) ◽  
pp. 4874 ◽  
Author(s):  
Linda Sequeira ◽  
John Nguyen ◽  
Liyun Wang ◽  
Anja Nohe
Keyword(s):  
Bone Mineral Density ◽  
Bone Formation ◽  
Bone Mineral ◽  
Single Photon ◽  
Femoral Shaft ◽  
Ovariectomized Rats ◽  
Sprague Dawley ◽  
Micro Computed Tomography ◽  
Mineral Density

Osteoporosis is a bone disease that has no definite cure. Current treatments for osteoporosis are divided into two categories: anti-resorptive and anabolic. However, these treatments are not perfect and have considerable risks. In addition, bone quality often declines over time with these treatments. We designed a peptide, CK2.3, that has both anabolic and anti-resorptive effects on bone. We reported that CK2.3 induced osteoblastic mineralization, promoted bone formation, and suppressed osteoclastogenesis in vivo. The effect of CK2.3 to rescue an osteoporosis phenotype model has never been shown. In this study, we demonstrated the effect of CK2.3 in ovariectomized rats, a standard model of osteoporosis. We systemically injected CK2.3 at 2.3 µg/kg each day for five consecutive days. Micro-computed tomography indicated that CK2.3 increased bone mineral density, (bone volume/tissue volume) BV/TV and (trabecular number) TbN, and decreased (trabecular space) TbSp in the femoral head. Similarly, single photon absorptiometry showed that treatment with CK2.3 increased bone mineral density in the lumbar spine and the pelvis. Additionally, we observed increased femoral shaft stiffness with ovariectomized rats treated with CK2.3. We also detected no significant changes in the weight of organs such as the heart, lung, liver, kidney, and spleen. An advantage of CK2.3 over current treatments was that it not only promoted bone formation but also improved fracture resistance. In conclusion, we demonstrated CK2.3 as a new anabolic treatment for osteoporosis.

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