scholarly journals Sirt1/Foxo Axis Plays a Crucial Role in the Mechanisms of Therapeutic Effects of Erzhi Pill in Ovariectomized Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Wenna Liang ◽  
Xihai Li ◽  
Guanhui Li ◽  
Liu Hu ◽  
Shanshan Ding ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Crucial Role ◽  
Molecular Mechanisms ◽  
Bone Biomechanics ◽  
Ovariectomized Rats ◽  
Therapeutic Effects ◽  
Bone Morphology ◽  
Mineral Density ◽  
Metabolism Disorder ◽  
Successful Establishment

Background. Erzhi pill (EZP), a traditional Chinese herbal formula, has been widely used to treat postmenopausal osteoporosis (PMOP) in China. However, its molecular mechanisms remain unclear. The aim of the present study is to investigate the antiosteoporotic effect of EZP on an ovariectomized rat model of PMOP. We performed the biomarkers of bone metabolism disorder, bone morphology, bone mineral density (BMD), and bone biomechanics to confirm the successful establishment of the PMOP model. We then investigated the expression of biomarkers related to the Sirt1/Foxo axis. We also examined microRNA-132 (miR-132), a regulator in the Sirtuin1 (Sirt1) expression. The bone metabolism disorder, bone morphology, BMD, and bone biomechanics in ovariectomized rats were improved by EZP administration. The antiosteoporotic effect of EZP was confirmed. We also found that the expressions of Sirt1, Runx2, Foxo1, and Foxo3a were downregulated in ovariectomized rats, while being then upregulated by EZP administration. And the expression of PPAR-γ and miR-132 was upregulated in ovariectomized rats and then downregulated by EZP administration. These results provided evidence that Sirt1/Foxo axis related mechanism may play a crucial role in the therapeutic effects of EZP, indicating that Sirt1/Foxo axis can be considered as a potential therapeutic target for PMOP in the future.

scholarly journals Effect of quercetin on bone metabolism and serum osteocalcin in osteoporotic rats

2020 ◽  
Vol 19 (2) ◽  
pp. 277-281 ◽  
Author(s):  
Hai Yang ◽  
Juntao Liu ◽  
Man Wang ◽  
Lu Wang ◽  
Lixiong Zhang ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Low Dose ◽  
Bone Biomechanics ◽  
Ovariectomized Rats ◽  
High Dose ◽  
Group Model ◽  
Serum Osteocalcin ◽  
Model Group ◽  
Mineral Density ◽  
Quercetin Treatment

Purpose: To determine the effect of quercetin on bone metabolism and serum osteocalcin in osteoporotic rats. Methods: Sixty specific pathogen-free rats were randomly divided into control group, model group; high, medium and low dose quercetin groups, and diethylstilbestrol group, with 10 rats in each group. The high, middle and low dose quercetin groups were given quercetin suspension at doses of 200, 100, 50 mg/kg/day, respectively; the ethylene estradiol group was given ethylene estradiol (1.0 mg/kg/week), while control rats received ethylene estradiol at doses of 200, 100, 50 mg/kg/day. Rats in the model group were given saline. Samples were taken after 6 weeks of administration. The levels of serum bone-derived alkaline phosphatase (BALP), estradiol (E2) and serum osteocalcin (BGP) in femur tissue were measured using ELISA kits. Bone mineral density (BMD) was determined using BMD tester. Results: Relative to normal rats, BALP and BGP levels in the model rats were markedly increased, while E2 was significantly lower (p < 0.5). Quercetin treatment led to significant increases in BALP and E2 levels in the middle and high dose groups, relative to the model group, while BGP levels in all quercetin treatment groups decreased significantly, when compared to model rats (p < 0.05). There were higher BMD values in quercetin and diethylstilbestrol groups than in model (p < 0.05). Conclusion: Quercetin enhances bone formation and BMD, but decreases osteocalcin levels and maintains bone biomechanics in ovariectomized rats. Thus, it may find therapeutic application in maintaining bone health. Keywords: Quercetin, Osteoporosis, Bone metabolism, Osteocalcin

Review of the Literature Examining the Association of Serum Uric Acid with Osteoporosis and Mechanistic Insights into Its Effect on Bone Metabolism

2019 ◽  
Vol 19 (3) ◽  
pp. 259-273 ◽  
Author(s):  
Neelam Kaushal ◽  
Divya Vohora ◽  
Rajinder K Jalali ◽  
Sujeet Jha
Keyword(s):  
Risk Factors ◽  
Bone Mineral Density ◽  
Uric Acid ◽  
Bone Metabolism ◽  
Serum Uric Acid ◽  
Bone Mineral ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Mineral Density ◽  
Age Related

Background And Objective:Osteoporosis is a common bone disorder that increases susceptibility to fragility bone fractures. The clinical and public health repercussions of osteoporosis are huge due to the morbidity, mortality, and cost of medical care linked with fragility fractures. Clinical assessment of osteoporotic risk factors can help to identify candidates at an early stage that will benefit from medical intervention and potentially lowering the morbidity and mortality seen with fractures and complications. Given this, research is ongoing to evaluate the association of osteoporosis with some novel or less well-studied risk factors/bio-markers such as uric acid (UA).Discussion:Uric acid’s antioxidant activity has been proposed to be one of the factors responsible for increasing longevity and lowering rates of age-related cancers during primate evolution, the level of which increased markedly due to loss of uricase enzyme activity (mutational silencing). Accumulated evidence shows that oxidative stress is the fundamental mechanism of age-related bone loss and acts via enhancing osteoclastic activity and increasing bone resorption. Antioxidant substances such as ascorbic acid scavenge free radicals are positively related to bone health. Thus, it is hypothesized that uric acid holds bone-protective potential owing to its potent antioxidative property. Several correlation studies have been conducted globally to investigate the relationship between serum uric acid with bone mineral density and osteoporosis. Few pre-clinical studies have tried to investigate the interaction between uric acid and bone mineral density and reported important role played via Runt-related transcription factor 2 (RUNX2)/core-binding factor subunit alpha-1 (CBF-alpha-1), Wingless-related integration site (Wnt)-3a/β-catenin signaling pathway and 11β Hydroxysteroid Dehydrogenase type 1.Conclusion:In this review, the authors provided a comprehensive summary of the literature related to association studies reported in humans as well work done until date to understand the potential cellular and molecular mechanisms that interplay between uric acid and bone metabolism.

scholarly journals Zhuang-Gu-Fang Treats Osteoporosis in Ovariectomized Rats by Increasing the Osteogenesis-Related Factors Leptin, Ghrelin, and PYY

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yuanjin Chen ◽  
Rui Bai ◽  
Wenhui Chen ◽  
Shuanglei Li ◽  
Yunxia Jiang
Keyword(s):  
Bone Metabolism ◽  
Therapeutic Effect ◽  
Wistar Rats ◽  
Dose Group ◽  
Bone Structure ◽  
Ovariectomized Rats ◽  
Type I ◽  
Mineral Density ◽  
Related Factors ◽  
Expression Levels

Zhuang-Gu-Fang is a Chinese medicinal compound mixture, which is mainly composed of traditional remedies like the Epimedium Herb, Astragalus, and Eucommia among many others. The study is aimed at investigating the therapeutic effect of Zhuang-Gu-Fang in ovariectomized rats. Fifty six-month-old Wistar rats were randomly selected and divided into 5 groups (n = 10), namely, model group, positive group, low-dose Chinese medicine group, medium-dose group, and high-dose group. Another 10 sham operation Wistar rats were taken as a negative control group. After 3 months of intervention, the bone mineral density (BMD), procollagen type I N-peptide (PINP), beta C-terminal cross-linked telopeptides of type I collagen carboxyl-terminal peptide (β-CTX), Leptin, Ghrelin, and Peptide YY (PYY) of each group were measured. Besides, the ultrastructure of bone structure and osteoblasts was also observed by transmission electron microscopy. Western blot method was used to detect the expression levels of Leptin and Ghrelin in bone tissue, and RT-PCR detected the mRNA expression levels of Leptin and Ghrelin. BMD test indicated that Zhuang-Gu-Fang could effectively prevent the loss of tibia bone in ovariectomized rats. Histomorphology analysis showed that Zhuang-Gu-Fang could preserve trabecular bone structure integrity and improve osteoblast ultrastructure. Notably, the study found out that Zhuang-Gu-Fang worked through balancing the bone metabolism via increasing bone formation/resorption ratio. Additionally, Zhuang-Gu-Fang highlighted the recovery effects in multiple levels of osteogenesis- and osteanagenesis-related factors Leptin, Ghrelin, and PYY. Conclusively, the study proved the therapeutic potential of the Zhuang-Gu-Fang for postmenopausal osteoporosis (PMOP) and further revealed that its therapeutic effect was related to the balance of bone metabolism and the recovery effects of bone-related factors Leptin, Ghrelin, and PYY.

scholarly journals Therapeutic Effects ofCortex acanthopanacisAqueous Extract on Bone Metabolism of Ovariectomized Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Zhiguo Zhang ◽  
Jiazi Dong ◽  
Meijie Liu ◽  
Yan Li ◽  
Jinghua Pan ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Control Agent ◽  
The Body ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Therapeutic Effects ◽  
Mineral Density ◽  
Ovx Rats

The aim of this study was to evaluate effects of aqueous extract fromCortex acanthopanacis(CAE) on osteoporosis rats induced by ovariectomy (OVX) using aqueous extract fromFolium Epimedii(FEE) as positive control agent. Three-month-old female rats that underwent OVX were treated with CAE. After 12 weeks, bone mineral density (BMD) and indices of bone histomorphometry of tibia were measured. Levels of protein and mRNA expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) in tibia were evaluated. In addition, the serum concentrations of osteocalcin (OC), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), calcitonin (CT), and parathyroid hormone (PTH) were determined. Administration of CAE significantly prevented OVX-induced rats from gain of the body weight. Treatment with CAE increased bone mass remarkably and showed a significant inhibitory effect on bone resorption by downregulating significantly the expression of RANKL in tibia of OVX rats. Meanwhile, treatment of CAE significantly reduced serum level of IL-1βand increased level of CT in OVX rats. This suggests that CAE has the potential to be used as an alternative therapeutic agent for postmenopausal osteoporosis.

Inducible Heme Oxygenase 1 (HMOX1) Promotes Osteoblastogenesis, and Inhibits Osteoclastogenesis and Myeloma-Induced Bone Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 627-627
Author(s):  
Xin Li ◽  
Sarah K. Johnson ◽  
Wen Ling ◽  
Sharmin Khan ◽  
Linda Saint John ◽  
...  
Keyword(s):  
Bone Disease ◽  
Molecular Mechanisms ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Therapeutic Effects ◽  
Human Mscs ◽  
X Rays ◽  
Mineral Density ◽  
Alizarin Red ◽  
Similar Treatment

Abstract Abstract 627 Cytotherapy with mesenchymal stem cells (MSCs) has been shown to promote bone formation, inhibit bone disease and reduce multiple myeloma (MM) growth in myelomatous bone (Yaccoby et al., 2006; Li et al., 2011). At the cellular level, the infused MSCs act as a bystander cells that activate endogenous osteoblasts and suppress osteoclast activity. To shed light on molecular mechanisms associated with the cytotherapeutic effects of MSCs we exploited the SCID-hu model engrafted with the Hg MM line. Hg cells are only maintained by passaging in SCID-hu/SCID-rab mice and produce severe bone disease. Human global gene expression profile (GEP) was performed in nonmyelomatous implanted bones (n=5), and in myelomatous implanted bones injected with human MSCs (1×106 cells/bone) and analyzed immediately (control group, n=8) or 24 hours later (cytotherapy, n=6). Based on stringent criteria, (e.g. ≥2 folds, p<0.05, signal intensity ≥500 in upregulated or downregulated genes in cytotherapy and control groups, respectively), approximately 60 genes were found to be upregulated and 50 genes downregulated in myelomatous bones 24 hours after cytotherapy. Among the top upregulated genes we identified HMOX1 (5 folds, p<0.03), an antioxidant factor known to be involved in anti-inflammatory and wound healing processes. HMOX1 expression was 4 folds lower in whole myelomatous bones compared to nonmyelomatous bones (p<0.0004) and its expression in myelomatous bones was restored to normal level 24 hours after MSC cytotherapy. Clinical biopsies from newly diagnosed MM patients (n=369) also had lower HMOX1 expression than biopsies from healthy donors (n=20) or MM patients in remission (n=92, p<0.0001), supporting our experimental findings. The Hg MM line expressed very low level of HMOX1 while cultured MSCs expressed high level of HMOX1. In vitro, treatment with the HMOX1 inducer, hemin (50 μM), for 24 hours upregulated HMOX1 expression in MM cells (n=9) by 58±32 folds (p<0.009). Similar treatment with hemin induced HMOX1 expression in osteoblast precursors by 10±0.04 folds (p<0.001) and in osteoclast precursors by 1.6 folds (p<0.06). Hemin had modest inhibitory effect on growth of myeloma cell lines in culture but markedly inhibited formation of multinucleated osteoclasts by 49±2% (p<0.0001) and induced mineralization of osteoblasts analyzed by alizarin red staining. For testing hemin effects on MM growth and bone disease, hosts engrafted with Hg MM line were treated with vehicle or hemin (9 mice/group, 50 μM in 500 μl/mouse/injection) twice a week for 3 weeks. Hemin treatment had no effect on in vivo growth of Hg MM cells; however, in control hosts, bone mineral density (BMD) of the myelomatous bone was reduced by 17±3% from pretreatment levels whereas in hemin-treated hosts BMD of the myelomatous bone was reduced by 2±3% (p<0.005). The protective effect of hemin on bone disease was also visualized on x-rays. These data suggest that HMOX1 upregulation by MSC cytotherapy is involved in the therapeutic effects of this intervention and that induction of HMOX1 expression in myelomatous bone by hemin inhibits MM-induced bone disease. Disclosures: Barlogie: Celgene, Genzyme, Novartis, Millennium: Consultancy, Honoraria, Patents & Royalties. Shaughnessy:Myeloma Health, Celgene, Genzyme, Novartis: Consultancy, Employment, Equity Ownership, Honoraria, Patents & Royalties.

scholarly journals Therapeutic effects of radix dipsaci, pyrola herb, and cynomorium songaricum on bone metabolism of ovariectomized rats

2012 ◽  
Vol 12 (1) ◽  
Author(s):  
Meijie Liu ◽  
Gary Guishan Xiao ◽  
Peijing Rong ◽  
Zhiguo Zhang ◽  
Jiazi Dong ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Ovariectomized Rats ◽  
Therapeutic Effects

Preventive and Therapeutic Effects of Acupuncture on Bone Mass in Osteopenic Ovariectomized Rats

2004 ◽  
Vol 32 (03) ◽  
pp. 427-443 ◽  
Author(s):  
Wenping Zhang ◽  
Masayuki Kanehara ◽  
Torao Ishida ◽  
Yi Guo ◽  
Xiuyun Wang ◽  
...  
Keyword(s):  
Lumbar Vertebrae ◽  
Ovariectomized Rats ◽  
Control Group ◽  
Acupuncture Points ◽  
Therapeutic Effects ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Trabecular Thickness ◽  
Ovx Rats ◽  
Model Control

This study was designed to (1) test the preventive and therapeutic effects of acupuncture on osteopenia in ovariectomized (OVX) rats, and (2) assess whether treatment of different acupuncture points causes different effects on tibiae, femora or lumbar spines. Thirty-five female Sprague-Dawley rats were divided into four groups: Sham (sham-operated, non-acupuncture); Model (OVX, non-acupuncture); Acp-A [OVX, bilateral needling of points Tsu-San-Li (ST-36) and San-Yin- Chiao (SP-6)]; and Acp-B (OVX, bilateral needling of P'i-Shu (Bl-20) and Shen Shu (Bl-23)). Operations were performed at 8 weeks of age, 1 week later the study was started and continued for 16 weeks. Ovariectomy resulted in decreased bone mineral density (BMD) compared to the sham group over time, and Acp-A tended to have higher BMD than the other OVX groups, especially for tibiae. In addition, the bone ash weight of the Acp groups tended to be heavier than the model group. Deoxypyridinoline, the urinary marker of bone resorption, also appeared to be decreased in both acupuncture groups. Similarly, microarchitecture and bone morphometry of lumbar vertebrae and tibiae, such as bone volume, trabecular thickness, trabecular number, mineralizing surface, bone formation rate, mineral apposition rate, number of nodes and number of node-terminus struts, also showed the same improvement in the acupuncture groups as compared to the model control group. Our findings showed that acupuncture may prevent the development of osteopenia in rats induced by ovariectomy. Needling of Tsu-San-Li (ST-36) and San-Yin- Chiao (SP-6) seems more effective than needling of P'i-Shu (Bl-20) and Shen Shu (Bl-23) in bone anabolic regulation.

scholarly journals Combined Extracts of Herba Epimedii and Fructus Ligustri Lucidi Rebalance Bone Remodeling in Ovariectomized Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Yuheng Chen ◽  
Xiaoxi Li ◽  
Xiufeng Tang ◽  
Yingying Gao ◽  
Ping Yu ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Molecular Mechanisms ◽  
Ovariectomized Rats ◽  
Tartrate Resistant Acid Phosphatase ◽  
Protective Effects ◽  
Mineral Density ◽  
Fructus Ligustri Lucidi ◽  
Maximal Load ◽  
Ovx Rats ◽  
Herba Epimedii

This study aimed to investigate the osteoprotective effect and the possible molecular mechanisms of the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi on postmenopausal osteoporosis (PMOP). Forty-eight female SD rats were sham-operated (Sham, n = 8) or ovariectomized (OVX, n = 40). Then after a week, OVX rats were divided randomly into five groups (n = 8 in each group): OVX, extracts of Herba Epimedii (HE, 0.35 g/kg), extracts of Fructus Ligustri Lucidi (FLL, 0.35 g/kg), combined extracts of HE and FLL (HE & FLL, 0.20 g/kg HE plus 0.15 g/kg FLL), and Raloxifene hydrochloride (RH, 6.25 mg/kg) groups. All groups were administered once daily for 12 weeks. Indicators related to bone remodeling were detected, including estradiol (E2), bone mineral density (BMD), maximal load, ultimate deflection, micro-CT properties, tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP) levels in serum and bone, and the protein and mRNA expression of bone turnover markers (RANKL, M-CSF, Wnt5a, Atp6v0d2, OPG, IGF-1, TGF-β1, and Bmp-2). Results showed that the combined extracts could increase serum E2 levels and BMD, enhance bone strength, reserve bone microstructure degeneration, promote bone formation, and inhibit bone resorption through upregulating the mRNA and protein expression of OPG, IGF-1, TGF-β1, and Bmp-2, while downregulating RANKL, M-CSF, Wnt5a, and Atp6v0d2. These findings demonstrated that the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi with bone protective effects on OVX rats might be an alternative medicine for the treatment of PMOP.

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