scholarly journals Icariin Treatment Enhanced the Skeletal Response to Exercise in Estrogen-Deficient Rats

Author(s):  
Zhao ◽  
Bu ◽  
Chen

Estrogen deficiency frequently leads to a fall in estrogen receptor- (ER) numbers and then reduces the skeletal response to mechanical strain. It, however, is still unclear whether phytoestrogen administration will enhance the effects of exercise on the estrogen-deficient bone loss. This study aimed to determine the effect of Icariin treatment on the response of osteogenic formation to exercise in ovariectomized (OVX) rats. Thirty-two 3-month old female Sprague–Dawley rats were randomly allocated into four groups: (1) Sham-operated (SO); (2) OVX; (3) OVX plus exercise (EX); and (4) OVX plus exercise and Icariin (EI). After 8-week interventions, the rats were killed and samples were collected for bone morphometry, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analyses. EI interventions showed a greater improvement for the OVX-induced bone loss and the elevated serum tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) compared with EX only. Both EX and EI interventions bettered the OVX-related reduction of BV/TV and trabecular number and thickness, and decreased the enlargement of trabecular bone separation (Tb. Sp); the improvement for BV/TV and Tb. Sp was greater in EI group. Furthermore, EX and EI treatment significantly increased the number of ALP+ cells and mineralized nodule areas compared with OVX group; the change was higher in EI group. Additionally, in comparison to OVX rats, the protein and mRNA expression of -catenin, phosphorylated-Akt (p-Akt) or Akt, ER, and Runt-related transcription factor 2 (Runx2) in osteoblasts were elevated in EX and EI intervention rats, with greater change observed in EI group. The upregulated -catenin and Akt mRNA levels in EX and EI groups was depressed by ICI182780 treatment, and the difference in -catenin and Akt mRNA levels between EX and EI groups was no longer significant. Conclusively, the combination of Icariin and exercise significantly prevent OVX-induced bone loss and increase osteoblast differentiation and the ability of mineralization compared with exercise alone; the changes might be regulated partly by ER/Akt/-catenin pathway.

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.


2021 ◽  
Author(s):  
Toshikazu Ito ◽  
Erquan Zhang ◽  
Ayaka Omori ◽  
Jane Kabwe ◽  
Masako Kawai ◽  
...  

Abstract Background: Preventing pulmonary vascular remodeling is a key strategy for pulmonary hypertension (PH). Causes of PH include pulmonary vasoconstriction and inflammation. This study aimed to determine whether cilostazol (CLZ), a phosphodiesterase-3 inhibitor, prevents monocrotaline (MCT)- and chronic hypoxia (CH)-induced PH development in rats.Methods: Fifty-one male Sprague-Dawley rats were fed rat chow with (0.3% CLZ) or without CLZ for 21 days after a single injection of MCT (60 mg/kg) or saline. Forty-eight rats were fed rat chow with and without CLZ for 14 days under ambient or hypobaric (air at 380 mmHg) CH exposure. Mean PAP (mPAP), the right ventricle weight-to-left ventricle+septum weight ratio (RV/LV+S), percentages of muscularized peripheral pulmonary arteries (%Muscularization) and medial wall thickness of small muscular arteries (%MWT) were assessed.Protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (peNOS), AKT, pAKT and IκB in lung tissue was measured by Western blotting. Monocyte chemotactic protein (MCP)-1 mRNA in lung tissue was also assessed.Results: mPAP [35.1±1.7 mmHg (MCT) (n=9) vs.16.6±0.7 (control) (n=9) (p<0.05); 29.1±1.5 mmHg (CH) (n=10) vs. 17.5±0.5 (control) (n=10) (p<0.05)], RV/LV+S [0.40±0.01 (MCT) (n=18) vs. 0.24±0.01 (control) (n=10) (p<0.05); 0.41±0.03 (CH) (n=13) vs. 0.27±0.06 (control) (n=10) (p<0.05)], and %Muscularization and %MWT were increased by MCT injection and CH exposure. CLZ significantly attenuated these changes in the MCT model [mPAP 25.1±1.1 mmHg (n=11) (p<0.05), RV/LV+S 0.30±0.01 (n=14) (p<0.05)]. In contrast, these CLZ effects were not observed in the CH model. Lung eNOS protein expression was unchanged in the MCT model and high in the CH model. Lung protein expression of AKT, phosphorylated AKT, and IκB was downregulated by MCT, which was attenuated by CLZ; the CH model did not change these proteins. Lung MCP-1 mRNA levels were increased in MCT rats but not CH rats.Conclusion: We found model differences in the effect of CLZ on PH development. CLZ might have a preventable effect on PH development in an inflammatory PH model but not in a vascular structural change model of PH preceded by vasoconstriction. Thus, the preventive effect of CLZ on PH development might be dependent on PH etiology.


2009 ◽  
Vol 87 (1) ◽  
pp. 51-55 ◽  
Author(s):  
Yong-Qi Li ◽  
Hui Ji ◽  
Yang Shen ◽  
Li-Ju Ding ◽  
Pei Zhuang ◽  
...  

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.


2021 ◽  
Vol 107 (4) ◽  
pp. 469-478
Author(s):  
H. Xie ◽  
L. Cao ◽  
L. Ye ◽  
G. Shan ◽  
W. Song

AbstractIn this study, the ability of microRNA-1906 (miR-1906) to attenuate bone loss in osteoporosis was evaluated by measuring the effects of a miR-1906 mimic and inhibitor on the cellular toxicity and cell viability of MC3T3‐E1 cells. Bone marrow-derived macrophage (BMM) cells were isolated from female mice, and tartrate-resistant acid phosphatase signalling was performed in miR-1906 mimic-treated, receptor-activated nuclear factor kappa-B (NF-κB) ligand (RANKL)-induced osteoclasts. In-vivo, osteoporosis was induced by ovariectomy (OVX). Rats were treated with 500 nmol/kg of the miR-1906 mimic via intrathecal administration for 10 consecutive days following surgery. The effect of the miR-1906 mimic on bone mineral density (BMD) in OVX rats was observed in the whole body, lumbar vertebrae and femur. Levels of biochemical parameters and cytokines in the serum of miR-1906 mimic-treated OVX rats were analysed. The mRNA expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), p-38 and NF-κB in tibias of osteoporotic rats (induced by ovariectomy) was observed using quantitative reverse-transcription polymerase chain reaction. Treatment with the miR-1906 mimic reduced cellular toxicity and enhanced the cell viability of MC3T3‐E1 cells. Furthermore, osteoclastogenesis in miR-1906 mimic-treated, RANKL-induced osteoclast cells was reduced, whereas the BMD in the miR-1906 mimic-treated group was higher than in the OVX group of rats. Treatment with the miR-1906 mimic also increased levels of biochemical parameters and cytokines in the serum of ovariectomised rats. Finally, mRNA expression levels of TLR4, MyD88, p-38 and NF-κB were lower in the tibias of miR-1906 mimic-treated rats than in those of OVX rats. In conclusion, the miR-1906 mimic reduces bone loss in rats with ovariectomy-induced osteoporosis by regulating the TLR4/MyD88/NF‐κB pathway.


2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Yinong Wang ◽  
Zhiwei Liu ◽  
Qing Wang ◽  
Qianjin Feng ◽  
Wufan Chen

This study aimed to investigate degradation of the articular cartilage and loss of the cancellous bone in an ovariectomized (OVX) rat model simulating early human menopausal stage. Fourteen health female Sprague-Dawley rats were randomly divided into two groups (n=7 per group): an OVX group that underwent bilateral ovariectomy to create an OVX model with low estrogen levels and a sham group in which only the periovarian fatty tissue was exteriorized. All the animals were sacrificed at 3 weeks after ovariectomy. The left tibiae were harvested. The articular cartilage at medial tibial plateau (MTP) and lateral tibial plateau (LTP) was assessed with quantitative high-frequency ultrasound. The cancellous bone was evaluated with micro-CT. The results indicated that, in comparison with the sham rats, the OVX rats exhibited significant alterations in acoustic parameters of the articular cartilage but insignificant changes in microarchitectural parameters of the cancellous bone in early stage of low estrogen levels. The results of this study suggest that cartilage degradation induced by estrogen reduction was detected earlier with quantitative ultrasound than that of the cancellous bone loss in 3 wk OVX rats.


2021 ◽  
Author(s):  
Nima Montazeri-Najafabady ◽  
Younes Ghasemi ◽  
Mohammad Hossein Dabbaghmanesh ◽  
Yousef Aashoori ◽  
Pedram Talezadeh ◽  
...  

Abstract Background Postmenopausal osteoporosis is a concern of health organizations, and current treatments do not seem enough. Postbiotics as bioactive compounds produced by probiotics may be an attractive alternative for bone health. In this study, we prepared, formulated, and compared the effects of cell lysate and supernatant of five native probiotic strains (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei, Bifidobacterium longum, and Bacillus coagulans) in ovariectomized (OVX) rats. Methods The probiotic strains were isolated, and their cell-free supernatants and biomasses as postbiotics were extracted and formulated using standard microbial processes. The Sprague-Dawley rats were fed by 1 × 109 CFU/ml/day postbiotic preparations and ovariectomized. Dual-energy X-ray absorptiometry (DEXA) scans were accomplished to evaluate femur, spine, and tibia BMD. The serum biochemical markers [calcium, phosphorus, and alkaline phosphatase] were assessed. Results Postbiotics could considerably improve the global and femur area in OVX rats. In the case of global BMC, Lactobacillus casei lysate and supernatant, Bacillus coagulans lysate and supernatant, lysate of Bifidobacterium longum and Lactobacillus acidophilus, and Lactobacillus reuteri supernatant significantly increased BMC. We found Bacillus coagulans supernatant meaningfully enriched tibia BMC. Conclusion Postbiotic could ameliorate bone loss resulting from estrogen deficiency. Also, the effects of postbiotics on different bone sites are strain-dependent. More clinical studies need to explore the optimal administrative dose and duration of the specific postbiotics in protecting bone loss.


2021 ◽  
Vol 18 (6) ◽  
pp. 1285-1289
Author(s):  
Fang Yu ◽  
QingNa Lv ◽  
ZhiHong Tong ◽  
WenJi Song ◽  
ZhengNan Zhao ◽  
...  

Purpose: To determine the potential effect of total flavonoids from Drynaria rhizome on bone loss in ovariectomized (OVX) rats. Methods: The rats were divided into four groups: normal control, ovariectomized (OVX) control, and two Drynaria rhizome (DR) flavonoids treatments. Post-operation, osteoporotic OVX rats were given Drynaria rhizome total flavonoids for 3 months. Thereafter, the expressions of bone-related genes and biochemical indices were investigated in samples taken from rat serum and bone. Results: Treatment with total flavonoids from Drynaria rhizome prevented bone mineral loss and improved some related biochemical indices associated with osteoporosis, namely, alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), bone gla protein (BGP) and estradiol (E2). Reverse transcription-polymerase chain reaction (RT-PCR) data showed that treatment with the total flavonoids significantly downregulated mRNA expression of Wnt10b, β-catenin, recombinant human bone morphogenetic protein-2 (BMP2) and BMP4 in OVX rats, but significantly reversed OVX-induced downregulation of dickkopf1 (Dkk1) mRNA expression. Conclusion: These results indicate that total flavonoids from Drynaria rhizome exert anti-osteoporotic effects in rats through the WNT signaling and BMP-2 signaling pathways.


2020 ◽  
Author(s):  
Daocheng Liu ◽  
Hao Qin ◽  
Jiazhi Yang ◽  
Lei Yang ◽  
Sihao He ◽  
...  

Abstract Background: Fractures in older men are not uncommon and need to be healed as soon as possible to avoid related complications. Anti-osteoporotic drugs targeting Wnt/β-catenin and PTH (parathyroid hormone) to promote fracture healing have become an important direction in recent years.Objective: Observe whether there is a difference in adult and aged situations by activating two signal paths.Methods: A single cortical hole with a diameter of 0.6 mm was made in the femoral metaphysis of Catnblox(ex3) mice and wild-type mice. The fracture healing effects of CA(Wnt/β-catenin activation) and PTH (activated by PTH (1–34) injections) were assessed by X-ray and CT imaging on days 7, 14, and 21 after fracture. The mRNA levels of β-catenin, PTH1R(Parathyroid hormone 1 receptor), and RUNX2(Runt-related transcription factor 2) in the fracture defect area were detected using RT-PCR. Angiogenesis and osteoblasts were observed by immunohistochemistry and osteoclasts were observed by TRAP (Tartrate-resistant Acid Phosphatase).Result: Adult CA mice and adult PTH mice showed slightly better fracture healing than adult wild-type (WT) mice, but there was no statistical difference. Aged CA mice showed better promotion of angiogenesis and osteoblasts and better fracture healing than aged PTH mice.Conclusion: The application of Wnt/β-catenin signaling pathway drugs for fracture healing in elderly patients may bring better early effects than PTH signaling pathway drugs, but the long-term effects need to be observed.


2018 ◽  
Vol 36 (3) ◽  
pp. 176-182 ◽  
Author(s):  
Xuefeng Zheng ◽  
Yan Nie ◽  
Chengtao Sun ◽  
Guangwen Wu ◽  
Qiaoyan Cai ◽  
...  

Background The pathogenic mechanisms of postmenopausal osteoporosis (PMOP) development are complex and are related to multiple cellular signalling transduction pathways. The aim of this study was to compare the effects of electroacupuncture (EA) at GV4/GV6 versus BL20/BL23 on the bones in ovariectomised (OVX) rats to explore the pathways that mediate the effects of EA on bone. Methods Forty female Sprague-Dawley rats were allocated to one of four groups (n=10 rats each) that received sham surgery (Sham group), OVX surgery only (OVX group), OVX surgery plus EA at GV4/GV6 (GV group) and OVX surgery plus EA at BL20/BL23 (BL group). Bone turnover markers osteocalcin (OC) and tartrate-resistant acid phosphatase 5b (TRACP 5b) were measured in serum, and bone mineral density (BMD) of the lumbar vertebrae and histomorphology of the femur were evaluated. Moreover, the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) was detected by ELISA. The expression of lipoprotein receptor-related protein (LRP) 5, β-catenin, runt-related transcription factor (Runx) 2 involving Wnt/β-catenin signalling and p38, c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 involving mitogen-activated protein kinase signalling were determined by Western blotting. Results The two EA-treated groups demonstrated increased levels of OC and the BMD of lumbar vertebrae, decreased levels of TRACP 5b and improved bone microstructure in the femur, compared with the untreated OVX group (P<0.05). Histomorphology analysis showed that EA treatment significantly increased the values of the trabeculae (µm), trabecular area (%) and trabecular bone number (per mm) and reduced trabecular separation (mm), compared with the OVX group. In addition, the ratio of OPG to RANKL and LRP5, β-catenin and Runx2 expression were significantly upregulated, while the expression of phosphorylated (p)-p38 and p-JNK were downregulated in EA-treated groups compared with the OVX group. Conclusion EA attenuates PMOP and it appears that the mechanism involves the regulation of multiple targets and pathways.


2021 ◽  
Vol 18 (7) ◽  
pp. 1513-1517
Author(s):  
ZhengNan Zhao ◽  
XiangLong Yang ◽  
Fang Yu ◽  
WenJi Song ◽  
HaiDong Liang

Purpose: To determine the potential effect of total flavonoids from Drynaria rhizome on bone loss in ovariectomized (OVX) rats. Methods: The rats were divided into four groups: normal control, ovariectomized (OVX) control, and two Drynaria rhizome (DR) flavonoids treatments. Post-operation, osteoporotic OVX rats were given Drynaria rhizome total flavonoids for 3 months. Thereafter, the expressions of bone-related genes and biochemical indices were investigated in samples taken from the serum and bone of the rats. Results: Treatment with total flavonoids from Drynaria rhizome prevented bone mineral loss and improved some related biochemical indices associated with osteoporosis: alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), bone gla protein (BGP) and estradiol (E2). Reverse transcription-polymerase chain reaction (RT-PCR) data showed that treatment with the total flavonoids significantly downregulated mRNA expression of Wnt10b, β-catenin, recombinant human bone morphogenetic protein-2 (BMP2) and BMP4 in OVX rats, but significantly reversed OVX-induced downregulation of dickkopf1 (Dkk1) mRNA expression. Conclusion: These results indicate that total flavonoids from Drynaria rhizome exert anti-osteoporotic effects in rats via WNT signaling and BMP-2 signaling pathways.


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