Eldecalcitol Plays a Role in Postmenopausal Osteoporosis through Mir-151a-3p/Socs5 Pathway

2021 ◽  
Vol 7 (5) ◽  
pp. 3934-3941
Author(s):  
Hongqing Zhang ◽  
Li Jia ◽  
Danzhi Li

Objective: This study set out to explore the specific mechanism of Eldecalcitol in postmenopausal osteoporosis (PMOP) and its relationship with miR-151a-3p/SOCS5 pathway. Methods: Forty-five rats were randomly and equally divided into sham operation group (SOG), model control group (MCG) and Eldecalcitol group (EG). miR-151a-3p, SOCS5 and bone mineral density (BMD) levels in each group were detected. MC3T3-E1 cells were modeled and divided into control group (CG), model group (MG) and EG. miR-151a-3p-inhibitor and pcDNA3.1-SOCS were transfected into model cells. miR-151 A-3P, SOCS5, RANKL and OPG levels as well as cell activity of cells in each group were observed. Results: Eldecalcitol intervention in rats can reduce BMD reduction caused by PMOP, reduce the miR-151a-3p level and increase the SOCS5 level. Cell experiments found that Eldecalcitol intervention can improve cell activity, inhibit the miR-151a-3p level and promote the SOCS5 expression, all of which can improve bone resorption of model cells, increase cell activity, inhibit the RANKL level and promote the OPG level. Conclusion: Eldecalcitol plays a role in PMOP by inhibiting miR-151a-3p and promoting the SOCS5 level.

2017 ◽  
Vol 242 (12) ◽  
pp. 1234-1243 ◽  
Author(s):  
Wu-Xun Peng ◽  
Chuan Ye ◽  
Wen-Tao Dong ◽  
Lei-Luo Yang ◽  
Chun-Qing Wang ◽  
...  

The study aims to investigate the effect of microRNA-34a (miR-34a) targeting Tgif2 on steroid-induced avascular necrosis of femoral head (SANFH) by regulating OPG/RANK/RANKL signaling pathway. SD rats were divided into normal control and model (RNAKL rat models) groups. The model group was further assigned into model control, negative control, miR-34a mimics and miR-34a inhibitors groups. QRT-PCR was applied to detect miR-34a, Tgif2, OPG, RANK and RNAKL mRNA expressions. Femoral head tissues were collected for Micro-CT scanning and HE staining. QRT-PCR and Western blotting were used to detect expressions of miR-34a, Tgif2, OPG, RANK, RANKL and Runx2, OPN and OC in bone tissues. Dual-luciferase reporter gene assay was used to testify the target relationship between miR-34a and Tgif2. Compared with the normal control group, the model group showed increased Tgif2, RANK and RANKL mRNA expressions, but decreased miR-34a and OPG mRNA expressions. Tgif2 mRNA expression was negatively correlated with miR-34a and OPG mRNA expressions. Micro-CT showed cystic degeneration of femoral head, with decreased bone volume/total volume (BV/TV), bone surface area/bone volume and trabecular number in the model control group compared with the normal control group. Compared with the model control group, the miR-34a mimics group showed increased BV/TV and trabecular thickness and Runx2, OPN and OC expressions, while the parameters decreased in the miR-34a inhibitors group. Compared with the normal control group, the other groups showed increased Tgif2, RANK and RANKL expressions but decreased miR-34a and OPG expressions. Compared with the model control group, Tgif2, RANK and RANKL expressions decreased and miR-34a and OPG expressions increased in the miR-34a mimics group, while the miR-34a inhibitors group had a reverse trend in contrast to the miR-34a mimics group. Tgif2 is a target gene of miR-34a. In conclusion, miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway. Impact statement miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway, which can be used as a new theoretical basis for SANFH treatment.


Marine Drugs ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. 652
Author(s):  
Liping Wang ◽  
Yiwen Hou ◽  
Rong Wang ◽  
Qi Pan ◽  
Debao Li ◽  
...  

This study investigates the inhibitory effect of astaxanthin (AST) on testosterone-induced benign prostatic hyperplasia (BPH) in rats. Except for the sham operation, BPH model rats were randomly assigned to five groups: the BPH model control rats, AST-treated BPH model rats (20 mg/kg, 40 mg/kg, and 80 mg/kg), and epristeride (EPR)-treated BPH model rats. After treatment, as compared with the BPH model control rats, the prostate and ventral prostate weights of the AST-treated rats decreased, while there was a marked decline in the 80 mg/kg AST-treated rats. The same effect was also observed in the prostate index and ventral prostate index. The proliferation characteristics of epithelia observed in the BPH model control group were gradually alleviated in the AST-treated rats. As compared with the BPH model control rats, lower epithelial thicknesses of prostates and fewer secretory granules in epithelia were observed in the AST-treated rats. The superoxide dismutase (SOD) activity of prostates increased in all the AST-treated rats with a significant increase in the 40 mg/kg and 80 mg/kg AST-treated rats. The testosterone (T) and dihydrotestosterone (DHT) levels of prostates in the AST-treated groups were lower than those in the BPH model control group, and a significant decline was found in the T level of prostates in the 40 g/kg and 80 mg/kg AST-treated rats and the DHT level of prostates in the 40 mg/kg AST-treated rats. These results indicate that AST might have an inhibitory effect on T-induced BPH in rats, possibly due to SOD activity regulation and T and DHT levels.


2021 ◽  
Author(s):  
Qian Zhang ◽  
Xu Yang ◽  
Ke Ma ◽  
Yanan Zhang ◽  
Xu Tian ◽  
...  

Abstract Background: Jingui Shenqi (JGSQ for short)pills is a traditional Chinese medicine formula, which has the functions of warming and tonifying kidney-yang, generating essence and filling marrow, warming tendons and veins and bones, and improving bone mineral density. The aim of this study was to investigate the effect and mechanism of JGSQ pills in preventing and treating postmenopausal osteoporosis.Methods : Twelve-week-old SPF female SD rats (n=48) were used in this study. Following the ovariectomy operation (n=40), the rats were randomly divided into the model group, (high, medium, and low dose groups) treated with Jingui Shenqi pills and estradiol group. Recorded the weight gain of rats and calculated the uterine coefficient; To detect the expression of serum calcium, phosphorus, ALP and OPG; HE staining was used to detect the pathological changes of femur; In all the groups, Micro-CT was used for detection of bone mineral density and bone microstructure; and gene expression of BMP-2, Smad1, and Runx2 in rat bone tissue was determined by RT-PCR and Western Blot methods.Results: Compared with the sham operation group, rats in the model group had the highest increase in body weight and the lowest uterine coefficient. Each of the treatment groups had a modest increase in weight gain. Micro-CT and HE staining showed a decrease in bone mineral density in the model group with shorter, thinner, broken, and osteoporotic trabeculae of the femur. The bone mineral density in Jingui Shenqi pills treatment groups had a significant increase with an improved bone microstructure and intact bone trabecular as compared to the model group. Serum ALP in the model group was significantly higher than in the sham operation group but the serum calcium, phosphorus and OPG was significantly lower. The Jingui Shenqi pills treatment groups and the estradiol treated group had lower serum ALP and increased serum calcium, phosphorus and OPG.There was decreased gene expression of BMP-2, Smad1, and Runx2 in the bone tissue of the model group compared to the sham operation group. BMP-2, Smad1, and Runx2 gene expression in Jingui Shenqi pills treated group and estradiol treated group was significantly higher than that of the model group.Conclusion: Jingui Shenqi pills improve the microstructure of bone tissue and increase bone mineral density thus resolving osteoporosis. This is achieved by regulating BMP/Smad signaling pathway and increasing the expression of osteogenic factors BMP-2, Smad1, and Runx2.


2014 ◽  
Vol 912-914 ◽  
pp. 1940-1943
Author(s):  
Yan Li ◽  
Xiao Ou Li ◽  
Feng Hao ◽  
Lei Zhang ◽  
Lei Liu ◽  
...  

To evaluate the control effect of Oviductus ranae on liver fibrosis in rats, and the change of TGF-β and α-SMA in liver of. To explore the mechanism of Oviductus ranae decoction on liver fibrosis. Methods Wistar female rats were randomly divided into a blank control group, model control group, colchicines group, Oviductus ranae group. Using the CCl4composite approach to make the rat modle. The course of treat-mart was 12 weeks.After treatment,All the rats was killed,and the materials and blood was taken,and to detect biochemical test of liver function after eight weeks. Investigating the variation of liver histology. Meanwhile detecting protein expression of TGF-β and α-SMA and by immunehistochemical method.Result The general condition of rats in all treatment groups are worse than the blank group,but better than the model group. And the rats in the model group were all occurred in liver fibrosis,and liver fibrosis is the most serious.In a normal rat liver tissue of TGF-β and α-SMA were significantly lower in model group and each treatment group, and there were significant differences, and the TGF-β and α-SMA in expression of liver tissue in model rats of TGF-β and α-SMA the highest. Conclusion: Oviductus ranae can effectively improve liver fibrosis rats induced by CC14liver function.Oviductus ranae can reduce the expression of TGF-β1in liver tissue of hepatic fibrosis rats induced by CCl4in. This may be one of the mechanisms of Oviductus ranae in prevention and treatment of liver fibrosis. Even though both increased expression of TGF-β and α-SMA expression, is able to determine TGF-β and α-SMA for the intervention of liver TGF-β signal transduction pathway in liver fibrosis.


2020 ◽  
Vol 10 (17) ◽  
pp. 6131
Author(s):  
Parkpoom Siriarchavatana ◽  
Marlena C. Kruger ◽  
Matthew R. Miller ◽  
Hong (Sabrina) Tian ◽  
Frances M. Wolber

The prevalence of metabolic osteoarthritis has been increasing worldwide, particularly among women. The aim of this study was to investigate the effects of the New Zealand greenshell mussel (Perna canaliculus; GSM) on osteoarthritis (OA) prevention in a rat model. One-hundred-and-eight female rats aged 12 weeks were divided into four test groups, containing 24 rats each, plus an additional control group. Each test group received one of the four experimental diets: normal control diet (ND), normal control diet supplemented with GSM (ND + GSM), high fat/high sugar diet (HFHS), or high fat/high sugar diet supplemented GSM (HFHS + GSM), for 36 weeks (end of the study). After 8 weeks on experimental diets, half of each group was subjected to ovariectomy (OVX) and the remaining half received a sham operation (ovaries left intact). The study evaluated body composition, bone mass, plasma cytokines, adipokines, HbA1c, CTX-II, and knee joint’s histopathology. HFHS diet and OVX significantly induced body weight gain and leptin production. OVX rats lost bone mineral density but increased adiponectin, HbA1C, and MCP-1. The OVX rats fed HFHS showed the highest Mankin scores. Importantly, inclusion of GSM reduced these pathological features. In conclusion, GSM might be beneficial in halting the progression of OA.


2019 ◽  
Vol 9 (6) ◽  
pp. 839-844
Author(s):  
Shuai Zhang ◽  
Weiwei Guo ◽  
Xin Zhao ◽  
Peng Li

Osteoporosis (OP) is a bone disease caused by various causes and can be found in various stages, such as juvenile, adult, menopausal and old age. OP has the systemic, degenerative, and metabolic characteristics, which leads to loss of bone mass, structural changes, and biomechanical properties degeneration. Prdx2 is a member of the peroxiredoxase family with antioxidant effects and involved in the regulation of bone and joint diseases. However, the role of Prdx2 in OP and related mechanisms has not been elucidated. SD rats were randomly divided into 2 groups, OP group in which OP rat model was prepared by ovariectomy and sham operation group. Prdx2 siRNA was transfected into OP rats followed by analysis of the expression of Prdx2, Opn, and Osterix by real-time PCR, bone density changes by dual energy line bone densitometer, formation of mineralized nodules by Alizarin red staining, Serum osteocalcin (OC) activity by ELISA as well as RANK and osteoprotegerin (OPG) expressions by real-time PCR and Western blot. Prdx2 expression was significantly increased, bone mineral density (BMD) was reduced, mineralized nodule formation was attenuated, Opn and Osterix levels were downregulated, together with decreased serum OC activity, increased RANK expression, and declined OPG expression apparently in OP rats compared with sham group (P < 0.05). Prdx2 siRNA transfection downregulated Prdx2 and RANK levels, increased BMD, mineralized nodule formation, Opn, OPG, and Osterix levels, as well as serum OC activity in OP rats (P < 0.05). Prdx2 expression is elevated in osteoporotic rats, which is associated with decreased osteogenic differentiation and BMD, leading to osteoporosis. Downregulation of Prdx2 expression can improve osteoporosis by regulating the RANK/OPG pathway.


2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Jizhong Zhao ◽  
Ke Cheng ◽  
Haiping Deng ◽  
Ling Zhao ◽  
Lanlan Liu ◽  
...  

Objective. To assess the effect of different lasers on cyclophosphamide- (CTX-) induced leucopenia in rats.Methods. 11 rats were normal control and 55 rats were injected with a dose of 80 mg/kg CTX for the first time and 40 mg/kg on the 6th and the 11th days to establish a leucopenia model. Rats of the irradiation groups received a 5-minute laser irradiation with either single 10.6 μm or 650 nm laser or alternatively 10.6 μm–650 nm laser irradiation, besides a sham treatment on acupoint Dazhui (DU 14) and acupoint Zusanli (ST 36) of both sides, 8 times for 16 days. Normal and model control group received no treatment.Results. On day 16 after the first CTX injection, the WBC counts from all the laser irradiation groups were significantly higher than those from the model control and the sham group (P<0.05), while there were no significant differences compared with the normal control (P>0.05). The TI of 10.6 μm–650 nm laser irradiation group was significantly higher than that of the model control group (P<0.05).Conclusions. The single and combined 10.6 μm and 650 nm laser irradiation on ST36 and DU14 accelerated the recovery of the WBC count in the rats with leucopenia.


2016 ◽  
Vol 3 ◽  
pp. 184954351667344
Author(s):  
Ya Di ◽  
Qingjie Meng ◽  
Hongwei Yang ◽  
Kun Li ◽  
Liyan Cao ◽  
...  

In this study, tanshinone was extracted from Salvia miltiorrhiza. To improve the utilization and the dissolution of the drug, the tanshinone extractions were prepared at a pharmaceutical nanoscale and in the nanometer range of 100–200 nm. Then, the rate of tumor inhibition and the activity of antioxidant system and the thymus/spleen indices were investigated to find the antitumor effect of nanoparticles of tanshinone in cervical carcinoma-bearing mice. Our data suggest that tanshinone inhibits cervical tumor growth and the rates of tumor inhibition of all drug groups were more than 45%. The highest rate was 70.88% in the high dose of nanoscale tanshinone group. The activities of superoxide dismutase were higher in drug groups than in the model control group, and the concentrations of malondialdehyde were significantly lower. These findings suggested that tanshinone enhance the superoxide dismutase activity of the mice and decrease the malondialdehyde content. It may be one of the mechanisms of antitumor effect of tanshinone. The thymus index and spleen index were higher than normal control or model control. These data suggested that tanshinone also enhanced the immune system of mice.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiangfeng Liu ◽  
Huijun Kang ◽  
Jiangfeng Lu ◽  
Yike Dai ◽  
Fei Wang

Abstract Background Poor osseointegration is the key reason for implant failure after arthroplasty,whether under osteoporotic or normal bone conditions. To date, osseointegration remains a major challenge. Recent studies have shown that deferoxamine (DFO) can accelerate osteogenesis by activating the hypoxia signaling pathway. The purpose of this study was to test the following hypothesis: after knee replacement, intra-articular injection of DFO will promote osteogenesis and osseointegration with a 3D printed titanium prosthesis in the bones of osteoporotic rats. Materials and methods Ninety female Sprague–Dawley rats were used for the experiment. Ten rats were used to confirm the successful establishment of the osteoporosis model: five rats in the sham operation group and five rats in the ovariectomy group. After ovariectomy and knee arthroplasty were performed, the remaining 80 rats were randomly divided into DFO and control groups (n = 40 per group). The two groups were treated by intraarticular injection of DFO and saline respectively. After 2 weeks, polymerase chain reaction (PCR) and immunohistochemistry were used to evaluate the levels of HIF-1a, VEGF, and CD31. HIF-1a and VEGF have been shown to promote angiogenesis and bone regeneration, and CD31 is an important marker of angiogenesis. After 12 weeks, the specimens were examined by micro-computed tomography (micro-CT), biomechanics, and histopathology to evaluate osteogenesis and osseointegration. Results The results of PCR showed that the mRNA levels of VEGF and CD31 in the DFO group were significantly higher than those in the control group. The immunohistochemistry results indicated that positive cell expression of HIF-1a, VEGF, and CD31 in the DFO group was also higher. Compared with the control group, the micro-CT parameters of BMD, BV/TV, TB. N, and TB. Th were significantly higher. The maximal pull-out force and the bone-to-implant contact value were also higher. Conclusions The local administration of DFO, which is used to activate the HIF-1a signaling pathway, can promote osteogenesis and osseointegration with a prosthesis in osteoporotic bone.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Demin Liu ◽  
Jing Wang ◽  
Haijuan Hu ◽  
Guoqiang Gu ◽  
Rui Ding ◽  
...  

Background. Hypertension contributes to the progression of cardiac remodeling and renal damage. In turn, renal sympathetic hyperactivation showed elevated sympathetic nervous system activity and led to blood pressure increase in certain patients. The purpose of this study was to observe the effect of renal nerve denervation on blood pressure and target organ changes in two hypertensive rat models. Methods. Hypertensive rats were randomly divided into a renal denervation (RDN) group and sham operation group. Wistar–Kyoto (WKY) rats of the same age were set as the baseline control group. In the secondary hypertension model, SD rats were randomly divided into five groups. Blood pressure and bodyweight were measured every week until they were euthanized. Results. The two rat models underwent RDN at key timepoints. At these timepoints, the hearts and kidneys were collected for norepinephrine and angiotensin II measurements and histological analysis. Conclusion. RDN performed before development of hypertension showed a significant antihypertensive effect on the secondary hypertension model.


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