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

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.

2011 ◽  
Vol 80 (4) ◽  
pp. 391-396 ◽  
Author(s):  
Iveta Gradošová ◽  
Helena Živná ◽  
Klára Švejkovská ◽  
Vladimír Palička ◽  
Aleš Tichý ◽  
...  

Amlodipine (dihydropyridine-type calcium channel blocker) is a widely used agent for the treatment of hypertension in human and veterinary medicine but detailed information about its effects on bone metabolism are missing. Therefore, the aim of our study was to investigate the effect of amlodipine on bone metabolism in male albino Wistar rats. Amlodipine (0.3 mg/100 g body weight; gavage) was administered to 8 rats for 8 weeks. Control group (n = 8) received aqua pro inj. (0.2 ml/100 g body weight; gavage). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I) and aminoterminal propeptide of procollagen type I in serum, and of bone alkaline phosphatase (BALP) in both serum and bone homogenate were measured by enzyme immunoassay. We investigated the expression of bone morphogenetic protein 2 (BMP-2) in proximal tibia using Western blotting, and bone mineral density was measured by Dual-energy X-ray Absorptiometry in lumbar and caudal vertebrae and in femoral areas. Mechanical properties of the femurs were measured by three-point bending of the shaft and compression testing of the femoral neck. After 8 weeks of amlodipine administration there was a significant decrease in serum concentrations of BALP (p = 0.0009) and CTX-I (p = 0.003), and the content of BALP in bone homogenate (p = 0.026) compared to the control. In addition, Western blot analysis indicated increased BMP-2 protein concentration after amlodipine administration. Our findings suggest that amlodipine has a retarding influence on bone metabolism in rats by decreasing bone turnover, which probably in consequence increases expression of BMP-2.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Wenna Liang ◽  
Xihai Li ◽  
Guanhui Li ◽  
Liu Hu ◽  
Shanshan Ding ◽  
...  

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.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1795-1795
Author(s):  
Chen Du ◽  
Gina Tran ◽  
Victorine Imrhan ◽  
Chandan Prasad ◽  
Parakat Vijayagopal ◽  
...  

Abstract Objectives The purpose of this study was to compare the effects of alpha tocopherol, gamma tocopherol, and the combination of alpha and gamma tocopherols on bone mineral density (BMD), bone mineral content (BMC), and bone metabolism in C57BL/6 J mice fed a high-fat diet. Methods A total of 75 male C57BL/6 mice were randomized to either a low fat diet (LFD) with 6% fat, a high fat diet (HFD) with 20% fat, HFD supplemented with alpha tocopherol (AT), gamma tocopherol (GT), or the combination of AT and GT. LFD and HFD were provided to corresponding groups of mice without vitamin E isoform supplements for 15 weeks to induce bone loss. At the end of the 15 weeks, AT, GT, and a combination of AT and GT were added to 3 of the HFD groups and fed for 10 weeks. LFD group and one of the HFD groups were continued on the same diet for another 10 weeks without additional supplements. All mice were euthanized at the end of the 25 weeks period. Left and right fibula bones were excised, cleaned, and scanned using the Lunar PIXImus dual-energy x-ray absorptiometry (DEXA) densitometer to assess BMD, BMC, lean tissue, and fat tissue content. Serum biomarkers of bone metabolism were evaluated post euthanization. Results HFD resulted in significantly lower fibular BMD and higher tibial bone fat content in comparison to LFD. Animals in the HFD supplemented with GT, but not AT, showed significantly reduced effect of HFD in lowering BMD. Additionally, in the group fed HFD supplemented with GT, a significantly higher concentration of alkaline phosphatase (ALP) and N-terminal propeptide of type I procollagen (PINP) were noted, compared to LFD. This may be indicative of increased bone formation resulting from GT incorporated into the HFD diet. Conclusions The findings of the study suggest that different isoforms of vitamin E affect bone density and bone metabolism differently. Within the different isoforms of vitamin E, gamma tocopherol may have protective effects in bone, especially in the situation of high fat diet induced bone loss. Further examination of the mechanistic action of vitamin E isoforms on skeletal health is warranted. Funding Sources Texas Woman's University.


2002 ◽  
Vol 93 (6) ◽  
pp. 2034-2037 ◽  
Author(s):  
H. Cavalié ◽  
G. Lac ◽  
P. Lebecque ◽  
B. Chanteranne ◽  
M.-J. Davicco ◽  
...  

This paper reports that the selective β2-adrenergic receptor agonist clenbuterol affects bone metabolism in growing 3-mo-old male Wistar rats treated over 8 wk. Thirty-two 3-mo-old growing Wistar rats weighing 234 ± 2 g were assigned to a progressive isometric force, strength-training exercise program plus oral clenbuterol (2 mg · kg body wt−1 · day−1) for 5 days each week, exercise program without clenbuterol 5 days each week, no exercise program plus oral clenbuterol (2 mg · kg−1 · day−1) for 5 days each week, or no exercise without clenbuterol 5 days each week. At the end of 8 wk, lean mass, fat mass, and right total femoral, distal metaphyseal femoral, and diaphyseal femoral bone mineral density were measured by Hologic QDR 4500 dual X-ray absorptiometry (DEXA) technique. Left femoral bones were harvested after death on day 58, and femoral resistance was determined by three-point bending testing. We found that fat mass was decreased in rats given strength training exercise and decreased further in rats treated with clenbuterol. Lean mass was increased in clenbuterol-treated animals. Strength-training exercise appeared to have no effect on bone mineral density, serum osteocalcin, or urinary deoxypyridinoline. However, clenbuterol treatment decreased femoral length, diameter, bone mineral density, and mechanical resistance. Clenbuterol had no effect on osteocalcin but increased urinary deoxypyridinoline. We concluded that clenbuterol treatment decreased bone mineral density and increased bone resorption independent of the level of exercise rats were given.


2006 ◽  
Vol 91 (11) ◽  
pp. 4453-4458 ◽  
Author(s):  
Mariateresa Sciannamblo ◽  
Gianni Russo ◽  
Debora Cuccato ◽  
Giuseppe Chiumello ◽  
Stefano Mora

Abstract Context: Patients with congenital adrenal hyperplasia (CAH) receive glucocorticoids as replacement therapy. Glucocorticoid therapy is the most frequent cause of drug-induced osteoporosis. Objective: The objective of the study was to evaluate bone mineral density (BMD) and bone metabolism in CAH patients. Design: This was a cross-sectional observational study. Setting: The study was conducted at a referral center for pediatric endocrinology. Patients and Other Participants: Thirty young patients with the classical form of CAH (aged 16.4–29.7 yr) treated with glucocorticoid from diagnosis (duration of treatment 16.4–29.5 yr) and 138 healthy controls (aged 16.0–30.0 yr) were enrolled. Main Outcome Measures: BMD was measured in the lumbar spine and whole body by dual-energy x-ray absorptiometry. Bone formation and resorption rates were estimated by serum measurements of bone-specific alkaline phosphatase and C-terminal telopeptide of type I collagen, respectively. Results: CAH patients were shorter than controls (women −6.8 and men −13.3 cm). Therefore, several methods were used to account for the effect of this difference on bone measurements. Whole-body BMD measurements were significantly lower, compared with controls (P < 0.03), after controlling for height (on average −2.5% in females and −9.3% in male patients). No differences were found in lumbar spine measurements. Bone-specific alkaline phosphatase and C-terminal telopeptide of type I collagen serum concentrations were higher in CAH patients than control subjects (P < 0.04). BMD measurements and bone metabolism markers did not correlate with the actual glucocorticoid dose or mean dose over the previous 7 yr. Conclusions: Young adult patients with the classical form of CAH have decreased bone density values, compared with healthy controls. This may put them at risk of developing osteoporosis early in life.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5052-5052 ◽  
Author(s):  
J. Mardiak ◽  
D. Ondrus ◽  
B. Spanikova ◽  
B. Ostatnikova

5052 Background: Improved survival of testicular cancer (TC) patients leads to rising of interest on late toxicity. Treatment-related bone loss is well recognized in breast and prostate cancer, but there has been little information in long-term survivors from other tumors. The aim of the study was to assign the damage of bone metabolism in TC patients. Materials: Bone mineral density (BMD) was measured by dual energy photon x-ray absorptiometry in the lumbar spine and hips. BMD was classified as osteopenia (T score ranging from -1 to -2,5) and osteoporosis (T score less -2,5). C-terminal cross-linked telopeptides of type I collagen (CTX) were measured using ELISA. Additionally serum total testosterone was measured. Comparison was made with matched control data. Relationships between baseline characteristics (age, treatment type and time from orchiectomy) and BMD were assessed using univariate and multivariate analysis tools. Results: We included 257 patients in the study (17 - 72 yrs old, median: 36 yrs) who were treated for GCT since 1982. 29 (11%) of them had bilateral orchiectomy (OE) due to bilateral TC. 23% of pts were treated by OE alone, 17% by subsequent radiotherapy of para-aortic field and 59% by subsequent chemotherapy. Median time since the OE was 4 years (1–36 yrs). Pts after bilateral OE had significantly lower BMD comparing with pts with unilateral OE. We didn’t find any differences between TC pts and matched control data regarding incidence of osteopenia and CTX, but the incidence of osteoporosis was considerably higher in TC pts. The incidence of osteoporosis appeared to increase with age and slightly correlated with time since OE, particularly after 10 years after OE. Type of therapy did not prove to have significant impact on the appearance of osteoporosis. Serum testosterone level did not correlate with BMD. Conclusion: The long term survivors from GCP have significantly higher risk of osteoporosis than healthy matched population. No significant financial relationships to disclose.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Shu-Jem Su ◽  
Yao-Tsung Yeh ◽  
Huey-Wen Shyu

Biochanin A (BCA) is a major isoflavone abundant in red clover (Trifolium pretense). The protective effect of BCA on bone loss in an ovariectomized (OVX) animal model has never been clarified. The objective of this study was to investigate the biological effects of BCA on bone loss in OVX ratsin vivoand on the development of osteoblasts and osteoclastsin vitro. Ovariectomy resulted in a marked increase in body weight and a decrease in femoral bone mineral density and trabecular bone volume that was prevented by BCA or 17β-estradiol (E2) treatment. However, an increase in uterine weight was observed in E2-treated OVX rats, but not in response to BCA treatment. Treatment with BCA increased the mRNA expression of osterix, collagen type I, alkaline phosphatase (ALP), and osteocalcin and decreased the mRNA expression of tartrate-resistant acid phosphatase (TRAP) and the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in the femur of OVX rats. Treatment with BCA or E2 prevented the OVX-induced increase in urinary deoxypyridinoline (DPD) and serum tumor necrosis factorα(TNF-α) and interleukin-1β(IL-1β).In vitro, BCA induced preosteoblasts to differentiate into osteoblasts and increased osteoblast mineralization. BCA inhibited preosteoclasts and osteoclast proliferation and decreased osteoclast bone resorption. These findings suggest that BCA treatment can effectively prevent the OVX-induced increase in bone loss and bone turnover possibly by increasing osteoblastic activities and decreasing osteoclastic activities.


2013 ◽  
Vol 305 (1) ◽  
pp. E15-E21 ◽  
Author(s):  
Stav Simsa-Maziel ◽  
Janna Zaretsky ◽  
Adi Reich ◽  
Yoav Koren ◽  
Ron Shahar ◽  
...  

The proinflammatory cytokine interleukin-1 (IL-1) signals through IL-1 receptor type I (IL-1RI) and induces osteoclastogenesis and bone resorption mainly during pathological conditions. Little is known about the effect of excess or absence of IL-1 signaling on the physiological development of the growth plate and bone. In this study, we examine growth plate morphology, bone structure, and mechanical properties as well as osteoclast number in IL-1RI knockout mice to evaluate the role of IL-1RI in the normal development of the growth plate and bone. We show for the first time that IL-1RI knockout mice have narrower growth plates due to a smaller hypertrophic zone, suggesting a role for this cytokine in hypertrophic differentiation, together with higher proteoglycan content. The bones of theses mice exhibit higher trabecular and cortical mass, increased mineral density, and superior mechanical properties. In addition, IL-1RI knockout mice have significantly reduced osteoclast numbers in the chondro-osseous junction, trabecular bone, and cortical bone. These results suggest that IL-1RI is involved in normal growth plate development and ECM homeostasis and that it is significant in the physiological process of bone modeling.


Author(s):  
RAMANDEEP KAUR ◽  
Makula Ajitha

Objective: In the present study, transdermal nanoemulsion (NE) gel of lovastatin was investigated for its anti-osteoporosis effect on the long bones of rat i.e. tibia. Methods: Male wistar rats (n=30, weighing 180-200g) were taken for this study and grouped as: 1) control (normal saline daily), 2) Dex (dexamethasone sodium; 25 mg/kg subcutaneously twice a week), 3) Dex+LNG5 (lovastatin nanoemulsion gel; 5 mg/kg/d transdermally daily), 4) Dex+LNG10 (lovastatin nanoemulsion gel; 10 mg/kg/d transdermally daily), and 5) Dex+ALN (alendronate sodium; 0.03 mg/kg/d orally daily). All the treatments were carried out for 60 d. At the end of the experiment, all animals were anesthetized using diethyl ether and collected blood samples from retro-orbital venous plexus of rats in dry eppendorf tubes followed by the sacrifice of animals by cervical dislocation method and collected tibia bones of both the legs for analysis. Results: Bone formation biomarkers (OC: osteocalcin, b-ALP: bone-specific alkaline phosphatase, PINP: N-terminal propeptides of type I procollagen) were significantly improved and resorption biomarkers (CTx: C-terminal cross-linking telopeptides of type-I collagen, TRAcP5b: isoform 5b of tartarate resistant acid phosphatase) were significantly reduced in the LNG5 (p<0.05) and LNG10 (p<0.05) treatment groups when compared to Dex. In vivo anti-osteoporotic results demonstrated the formation of new bone in osteoporotic rat tibias. Biomechanical strength testing demonstrated increased load-bearing capacity of rat tibias in the treated animals in comparison with the osteoporotic group (p<0.05 for LNG5 and p<0.01 for LNG10). Conclusion: Thus, the transdermal NE gel formulation of lovastatin demonstrated the greater potential for the treatment of osteoporosis.


2001 ◽  
Vol 91 (4) ◽  
pp. 1663-1668 ◽  
Author(s):  
K. J. Hart ◽  
J. M. Shaw ◽  
E. Vajda ◽  
M. Hegsted ◽  
S. C. Miller

Weight-bearing exercise is traditionally recommended for improving bone health in postmenopausal women. Effects of swim exercise were studied as an alternative to weight-bearing exercise in ovariectomized rats. Rats in a swim group (Sw, n = 8) swam for 12 wk, 5 days/wk for 60 min per session. A control group (Con, n = 9) engaged in no structured exercise. Femurs were analyzed for bone mineral density and for bone mineral content by dual energy X-ray absorptiometry, biomechanical properties by three-point bending (Instron), and bone structure and formation by histomorphometry. Food intake did not differ among groups. Final body weights were significantly lower in Sw compared with Con ( P< 0.05). Swimmers had significantly greater femoral shaft bone mineral density and content ( P < 0.05) compared with Con. Femurs of the Sw group had greater mechanical properties ( P< 0.05) compared with Con. Histomorphometric data were significantly better in the Sw group compared with Con after the 12-wk intervention ( P < 0.05). In conclusion, data from this study demonstrate some beneficial effects of swim exercise on bone structure, turnover, and strength.


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