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Since December 2019,severe acute respiratory syndrome coronavirus 2 has been found to be the culprit in the coronavirus disease 2019 (COVID-19),causing a global pandemic.Despite the existence of many vaccine programs,the number of confirmed cases and fatalities due to COVID-19 is still increasing.Furthermore,a number of variants have been reported.Because of the absence of approved anti-coronavirus drugs,the treatment and management of COVID-19 has become a global challenge.Under these circumstances,drug repurposing is an effective method to identify candidate drugs with a shorter cycle of clinical trials.Here,we summarize the current status of the application of drug repurposing in COVID-19,including drug repurposing based on virtual computer screening,network pharmacology,and bioactivity,which may be a beneficial COVID-19 treatment.
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Thioredoxin-interacting protein ( TXNIP) suppresses the antioxidative function of thioredoxin ( Trx ) by combining with thioredoxin ( Trx).Therefore, it promotes the generation and accumulation of reactive oxygen species ( ROS ) , inducing endoplasmic reticulum stress and mitochondrial stress , which leads to cellular inflammation or cellular apoptosis ultimately . TXNIP-mediated oxidative stress plays a crucial role in control-ling the generation and development of some diseases , such as diabetes and its complications ( diabetic nephropathy diabetic retinopathy etc .) , atherosclerosis ischemia/reperfusion injury , cancers ( hepatocellular carcinoma , carcinoma of urinary blad-der, mammary cancer , leukemia ) etc.Here, we try to review the action and mechanism of oxidative stress mediated by TXNIP in the diseases and the progress in research .
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Aim To investigate the effects of dalbinol on proliferation and apoptosis of human colon cancer HCT1 16 cells and its mechanisms.Methods Anti-proliferative effect of dalbinol was evaluated by MTT assay.The morphological changes of apoptosis were observed by Hoechst33342 staining.Apoptotic rate and ROS generation were analyzed by flow cytometry.The related proteins of Wnt/β-catenin pathway and the ap-optosis-associated proteins expression were measured by Western blot.Results The growth of HCT1 16 treated with dalbinol was inhibited in a dose and time dependent manner with IC50 (4.8 ±0.53 ),(2.5 ± 0.43)and (0.6 ±0.22)μmol·L-1 at 24,48 and 72 h,respectively.Typical morphological changes of ap-optosis such as cell shrinkage,karyopyknosis and nu-clear condensation were observed by Hoechst33342 staining.Meanwhile,the apoptotic rate and intracellu-lar ROS generation of dalbinol were both increased dose-dependently. Western blot results showed that dalbinol could activate the expression of cleaved Caspase-3 and cleaved PARP by decreasing anti-apop-totic protein levels such as Bcl-2 and Mcl-1 and in-creasing pro-apoptotic protein levels such as Bax and Bim,which induced further apoptosis.Moreover,dal-binol can reduce the protein expression of the total and nuclear β-catenin,but not cytoplasmic β-catenin by suppressing the protein expression of Dvl-2 and GSK-3β(pS9 ),as well as its target proteins c-Myc and Sur-vivin.Conclusion dalbinol can induce apoptosis in colon cancer HCT1 16 cells by upregulating the intra-cellular ROS generation and suppressing Dvl/GSK-3β/β-catenin pathway.
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Genistein, as one kind of phytoestrogens, can stimu-late osteoblastic proliferation, differention and mineralization, and can also inhibit bone resorption activity of osteoclast. The effect of genistein on bone metabolism lies in various molecular mechanisms. This paper reviews the research progress of the an-ti-osteoporotic action of genistein and its mechanism, which may provide a basis for the research and development of new agents to treat osteoporosis.
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Aim To investigate the effects of red yeast rice capsules containing coenzyme Q10 on femur with an animal model of osteoporosis, which was induced by OVX with D-galactose in rats, and the results were compared with those obtained from diethylstilbestrol. Methods Three-month old female Sprague-Dawley rats were randomly divided into sham group ( CON ) , ovariectomized group ( OVX ) , model group ( MOD ) , diethylstilbestrol group( DES) , and red yeast rice cap-sule group( RYR) . After 60 days, the left femurs were collected for Ca, P and hyp measurement, while the right femurs were performed with three-point bending test and micro-CT evaluation, respectively. Results Compared with CON group, MOD group had a signifi-cant increase in body weight, Tb. Sp, SMI and signifi-cant decrease in maximum load, stiffness, maximum strength, break strength, elastic modulus, Ca, P, Hyp contents and indicators of BV/TV, Tb. N, BMD, Conn-Dens. On the other hand, compared with MOD group, RYR group had a lower body weight and all bone biomechanics indexes were increased without sta-tistically significant difference. At the same time, the content of Ca, P and indicators of BV/TV, Tb. N, Tb. Th, BMD, Conn-Dens increased significantly;yet Tb. Sp decreased significantly. In DES group, the results of indicators were consistent with those for RYR group. In addition, compared with DES group, in RYR group body weight decreased significantly;the content of Ca, P and indicators of BV/TV, Tb. N, Tb. Th, Conn-Dens were significantly higher, and Tb. Sp, SMI were significantly lower. Conclusions Significant bone loss and deteriorated mechanical properties of femur can be observed in animal model of osteoporosis induced by OVX combined with D-galactose. Red yeast rice cap-sules containing coenzyme Q10 show effective prevention effects. Furthermore, red yeast rice capsules(0. 5 tab-let·kg-1 ) have better effect on increasing the number of trabecular bone than diethylstilbestrol ( 30 μg · kg-1 ) does.
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Salvia miltiorrhiza is a traditional Chinese medicine for the treatment of cardiovascular diseases .Recently, increasing evidence demonstrates that the water-soluble compounds isolated from Salvia miltiorrhiza,including tanshinol and salvianolic acid B, exert a regulatory influence on bone metabolism .The under-lying mechanism of these compounds involves various pathways , such as Wnt/β-catenin, ERK, BMP, OPG/RANKL/RANK and FoxO mediated oxidative stress pathway .This paper reviews pre-vious effects and mechanism of polyphenolic acids in Salvia milt-iorrhiza , which may provide the base for the research and devel-opment of the new agents to treat osteoporosis .
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Aim To investigate the preventive effect of Polygonum Multiflorum (PM)on the deteriorated mi-cro-structure and biomechanical properties induced by prednisone.Methods Ninety 6-month-old male Sprague-Dawley rats were randomly divided into nine groups,which were control,prednisone,CAL,30%ethanol eluent of the PM(H,M,L),PM(H,M,L). Prednisone was gavaged to rat for 21 weeks as model group of osteoporosis.Meanwhile,tested herbal ab-stract were orally administrated to the modeled rats in-duced by prednisone.At the end of the experiment, the right femur was collected for micro-CT scanning, three-dimensional reconstruction and biomechanical test.Results Compared with the control group,mod-el group showed destruction of bone microarchitecture, BV /TV fell 28.6%(P <0.05),bone biomechanical parameters decreases,and stiffness fell 29.7%(P <0.01 ). Compared with the model group, positive group had significantly improved effect on bone micro-architecture,and biomechanical parameters,BV /TV increased 46.7%(P <0.01 ),and stiffness increased 25.9%(P <0.01 ).30% ethanol eluent of the PM (M,L)dose may improve bone microstructure by in-creasing BV /TV 46.7% (P <0.01 ),40.0% (P <0.05)respectively,PM(H)may improve the biome-chanical parameters by increasing stiffness 24.7%(P<0.05),and 30% ethanol eluent of the PM(H)and PMhigh-dose may improve the biomechanical parame-ters,but not as positive group.Conclusions Predni-sone reduces biomechanical properties of rat femur and deteriorates femoral microstructure.30% ethanol eluent of the PM(M,L)and PM(H)plays a preventive role in the changes of micro-structural and biomechanical properties by prednisone,and increases BMD,whereas other groups have no significant preventive effect.
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Aim To investigate the effect of tanshinol on bone mineral density and microstructure of proximal tibias in rats with bone loss induced by glucocorticoid. Methods Sixty 7-month-old female SPF SD rats were randomly divided into 6 groups with 1 0 rats per group:control group(saline:5 ml·kg -1 ·d -1 ),glucocorti-coid group (prednisone acetate:6 mg·kg -1 ·d -1 ), glucocorticoid +low dose of tanshinol group(1 2.5 mg ·kg -1 ·d -1 ),glucocorticoid +medium dose of tan-shinol group (25 mg·kg -1 ·d -1 ),glucocorticoid +high dose of tanshinol group (50 mg·kg -1 ·d -1 ), glucocorticoid +(positive control drug)calcitriol group (0.045 μg · kg -1 · d -1 ).Rats were gavaged with prednisone acetate continuously for 1 4 weeks to estab-lish the bone loss model.Meanwhile,tanshinol and calcitriol were orally administered to the rats which were treated with prednisone acetate for intervention. At the end of the experiment,the left proximal tibias were collected for Micro-CT scanning and three-dimen-sional reconstruction of cortical and trabecular bone re- spectively to observe the changes of bone microstruc-ture and test related parameters.Results Bone min-eral density was decreased and bone microstructure was destroyed in proximal tibias of rats after treatment with glucocorticoid.Both tanshinol (25 mg·kg -1 ·d -1 ) and calcitriol(0.045 μg·kg -1 ·d -1 )could increase bone mineral density and improve bone microstructure in proximal tibias without significant differences be-tween each other.Tanshinol (50 mg · kg -1 · d -1 ) could improve bone microstructure to some extent,but it had no significant effect on bone mineral density. Tanshinol(1 2.5 mg·kg -1 ·d -1 )had no significant effect on bone mineral density or microstructure.Con-clusion Oral administration of tanshinol (25 mg · kg -1 ·d -1 )to the rats treated with glucocorticoid can increase bone mineral density and improve bone micro-structure in proximal tibias.
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Objective:o prepare Danshensu liposomes and investigate drug release characteristics in vitro. Methods: Danshensu liposomes were prepared by a reverse-phase evaporation method. The encapsulation efficiency was used as the index, an orthogonal test was adopted to investigate the effect of concentration of soybean lecithin, ratio of lipid-Danshensu and pH value of solution on the preparation procedure of Danshensu liposomes. The particle size of the liposomes was also investigated by a transmission electron micro-scope ( TEM) . The concentration of Danshensu was determined by HPLC, and the difference of release characteristics in Danshensu li-posomes and Danshensu solution was measured by a dialysis method. Results:The optimum preparation technology was as follows:the concentration of soybean lecithin was 40 mg·ml-1 ,the ratio of drug-lipid was 1: 10,and the pH value of solution was 6. 6. The mor-phology of the prepared liposomes showed spheric structure with uniform diameter, and the average particle size was ( 174 ± 36 ) nm and the encapsulation efficiency was 38. 9%. The linear range of Danshensu was 2. 0-20. 0 mg·L-1(r=0. 9984). The drug release of liposomes in vitro was slower than that of free Danshensu solution in 24 h. Conclusion:Danshensu liposomes with fine morphology have sustained release property.
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<p><b>OBJECTIVE</b>To investigate the correlation between regulatory T (Treg) cells and postmenopausal osteoporosis and the antiosteoporotic effect of 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃] in relation to Treg cells.</p><p><b>METHODS</b>Fifty female BALB/c mice were randomly divided into five groups: the basal control (BAS), Sham, ovariectomy (OVX), OVX+diethylstilbestrol (OVX+DES), and OVX+1,25(OH)₂D₃. Tibias were harvested and processed with decalcification for quantitative bone histomorphometry. Femurs were stained by immunohistochemistry to detect Foxp3 protein expression. Spleens were used to detect Treg and Foxp3 gene expression by flow cytometry and quantitative RT-PCR, respectively.</p><p><b>RESULTS</b>In comparison with the Sham group, a significant decrease was found in the OVX group in such indices as trabecular bone volume/total tissue area (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th). 1,25(OH)₂D₃and DES partly prevented the decrease in BV/TV, Tb.N, Tb.Th in OVX mice. Treg cell number, Foxp3 mRNA expression in spleen and Foxp3 protein expression in femur significantly decreased in the OVX-treated group compared with those in the sham group. 1,25(OH)2D₃and DES significantly increased Treg cell number and Foxp3 expression. Treg cells and Foxp3 gene expression were related to bone histomorphometric parameters.</p><p><b>CONCLUSION</b>The decrease in Treg cell numbers is relevant to the postmenopausal osteoporosis. The antiosteoporosis of 1,25(OH)₂D₃is related to regulatory T cells.</p>
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Animals , Female , Mice , Bone Density Conservation Agents , Pharmacology , Therapeutic Uses , Calcitriol , Pharmacology , Therapeutic Uses , Gene Expression Regulation , Mice, Inbred BALB C , Osteoporosis , Drug Therapy , Ovariectomy , T-Lymphocytes, RegulatoryABSTRACT
Aim To investigate whether D-galactose cause osteoporosis and the difference compared with the osteoporosis induced by ovariectomy, and to deter-mine whether ovariectomy coupled with D-galactose ac-celerated the progress of osteoporosis and whether es-trogen had a preventive effect on these osteoporosis models. Methods Sixty SPF mice were randomly divided into six groups , namely sham-operated group, D-galactose group, OVX group, OVX + D-galactose group, OVX + D-galactose + diethylstilbestrol group and D-galactose + diethylstilbestrol group. Seventy days later, the right tibia was processed with undecal-cified sections for bone histomorphometric analysis. Results Compared with the sham-operated group, %Tb. Ar, Tb. Th and Tb. N decrease by 50. 4%, 25. 4%, 50. 9% ( P <0.01 ) respectively, Tb. Sp in-creased by 169. 4% (P <0.05), Oc. pm, Oc. No. ,%Oc. S, Oc. N/mm which reflected bone absorption significantly increased ( P < 0.01 ) , and % L. Pm, MAR, BFR/TV, BFR/BV, BFR/BS which reflected bone formation significantly decreased ( P <0.01 ) in OVX group. %Tb. Ar decreased by 30. 4% in D-ga-lactose group, but there was no statistically significant difference. However, the four parameters reflected the bone absorption in D-galactose group increased signifi-cantly ( P<0.05 ) , while the four parameters reflected bone formation decreased significantly ( P < 0.05 ) . OVX+D-galactose group has obvious performance of osteoporosis, but there was no significant difference compared to OVX group, nor to D-galactose group. Estrogen had significant preventive effect on related pa-rameters of osteoporosis induced by D-galactose and o-variectomy coupled with D-galactose. ConclusionsOsteoporosis model of mice can be established by OVX, D-galactose and OVX +D-galactose. Estrogen can effectively prevent bone loss induced by D-galac-tose and OVX+ D-galactose.
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In order to make the experimental teaching adapt to the development of modern teaching idea and to meet the needs of the pharmaceutical industry for high quality talents, pharma-cology experiment teaching method has been reformed. Single teaching method has turned to diversi-fied teaching method according to the experimental contents, difficulty and characteristics of teaching situation, such as leading method of using theory after experiment in validation experiments and single blind method in multidrug efficacy experiment in the early stage, case-based teaching in comprehensive experiments in the middle stage , and student teaching method in designing experiments in the later stage. The study results show that students' interest in learning has been inspired,their experimental enthusiasm has been mobilized,and their operation, analysis and problem-solving ability has been improved, which is advantageous to the comprehensive quality education.
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Aim To investigate the effects of predni-sone on trabecular microstructure and biomechanical properties of femur in a rat model of type II collagen-induced arthritis (CIA ) using micro-CT and biome-chanics.Methods Forty 8-week-old male Lewis rats were randomly divided into 2 groups:control (CON ) group with 6 rats,and the remaining 34 rats were used to establish the CIA model.3 weeks after immunization screening CIA rats were randomly divided into CIA group,CIA plus prednisone 4.5 mg · kg-1 · d -1 group and CIA plus prednisone 9 mg · kg-1 · d -1 group.Rats in CON group were given vehicle as well as in CIA group.Rats in the other two groups were treated with prednisone at 4.5 mg·kg-1 ·d -1 or 9 mg ·kg-1 · d -1 .After 90 days treatment,all rats were euthanized,and the left femur was collected for biome-chanics,micro-CT scanning and three-dimensional re-construction.Results Micro-CT data showed that tra-becular thickness,trabecular number,bone volume/total volume,bone mineral density in CIA group were significantly lower than those in CON group.While tra-becular separation,structure model index were signifi-cantly higher than those in CON group.Compared with CON group,biomechanical properties (elastic load, maximum load,break load and stiffness)were signifi-cantly decreased in CIA group.Compared with CIA group,bone volume/total volume and trabecular num-ber were increased,while trabecular separation was significantly decreased in two prednisone groups.Com-pared with CIA group,there was no significant change in biomechanical properties in two prednisone groups. Conclusions Treatment with prednisone for 3 months can ameliorate the damage of trabecular microstructure of the femur in CIA rats,but it has no effect on biome-chanical properties and bone mineral density.
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The aim of this study is to investigate the effects of electrical stimulation ES) on the induction of rat bone marrow mesenchymal stem cells (rBMSCs) to differentiate into cardiomyocyte-like cells in vitro. The third or fourth-generation of the rBMSCs was randomly divided into three groups, i. e. ES group, 5-Azacytidine (5-Aza) group, and control group. Those in the ES group with complete medium were exposed to 1,2,4 and 6V, 2Hz, 5ms ES for 2h everyday,lasting for 10d. Those in the 5-Aza group were induced by 10 micromol/L 5-Aza for 24h, then the medium was changed to complete medium without 5-Aza. Those in the control group were only cultured with complete medium. The growth status and morphological features of rBMSCs were observed by inverted phase microscope. The mRNA expressions of GATA4, a-actin, ACTN2 and TNNT2 were determined by Real-time fluorescent quantification PCR, and the protein expression of TNNT2 was detected with immunofluorescence staining. The results showed that the mRNA expression level of the GATA4, a-actin, ACTN2 and TNNT2 and the protein expression level of the TNNT2 were significantly higher in the ES group and 5-Aza group, compared to those in the control group(P<0. 05). It suggested that ES could induce rBMSCs differentiation into cardiomyocyte-like cells in vitro.
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Animals , Female , Male , Rats , Bone Marrow Cells , Cell Biology , Cell Differentiation , Cell Proliferation , Cells, Cultured , Electric Stimulation , Mesenchymal Stem Cells , Cell Biology , Myocytes, Cardiac , Cell Biology , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To study whether effect of aspirin plus low-dose diethylstilbestrol is more effective and safer than high diethylstilbestrol dose alone on prevention of ovariectomy-induced osteopenia and dyslipidemia.</p><p><b>METHODS</b>Thirty-eight 4-month-old female SD rats were divided into baseline (BAS) group (n=6), sham operation group (n=8) and ovariectomy (OVX) group (n=24). The OVX group was further divided into vehicle treatment group (n=8), diethylstilbestrol (30 μg/kg•d) treatment group (OVX+D30 group, n=8), and aspirin (9 mg/kg•d) plus diethylstilbestrol (10 μg/kg•d) treatment group (OVX+A-D10 group, n=8). Their left tibiae were collected for the bone histomorphometric analysis in undecalcified sections. Left femurs were collected for the bone mineral density measurement.</p><p><b>RESULTS</b>The body weight and serum cholesterol were increased, while uterine weight and cancellous bone mass were decreased in OVX rats compared with the SHAM group. Cancellous bone mass was significantly increased, while body weight and bone resorption parameters were decreased in both A-D10 and D30 treatment group compared with OVX group. The rats treated with A-D10 showed significantly increased in bone formation parameters and decreased in serum triglyceride compared with the D30-treated rats.</p><p><b>CONCLUSION</b>Aspirin plus low-dose diethylstilbestrol can effectively prevent osteopenia by reducing bone resorption, and is thus a better treatment modality for preventing dyslipidemia than high-dose diethylstilbestrol alone.</p>
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Animals , Female , Rats , Anti-Inflammatory Agents, Non-Steroidal , Pharmacology , Therapeutic Uses , Aspirin , Pharmacology , Therapeutic Uses , Biomarkers , Blood , Body Weight , Bone Density , Bone Diseases, Metabolic , Blood , Bone and Bones , Diethylstilbestrol , Pharmacology , Therapeutic Uses , Drug Evaluation, Preclinical , Drug Therapy, Combination , Dyslipidemias , Blood , Estrogens, Non-Steroidal , Pharmacology , Therapeutic Uses , Organ Size , Ovariectomy , UterusABSTRACT
This study was aimed to investigate the effects of different doses of dexamethasone (Dex) on bone quality in rats. Thirty-one SD rats were randomly divided into 4 groups, Control (7 with saline), Dex-L (8 with 1 mg Dex. / kg), Dex-M (8 with Dex. 2.5 mg/kg), Dex-H (8 with Dex. 5 mg/kg), with tail injection, twice per week for 8 weeks. All the rats were killed then. Their proximal tibia were processed into undecalcified sections and measured for bone histomorphometry. The content of Ca2+ and hydroxyproline in their left ulnars were tested. Bone mineral density (BMD) and biomechanical property of the thigh bone were tested to observe the qualities of bone. Compared to the control group, the bodyweights of the rats in different Dex treatment Groups decreased remarkably. Percent labeled perimeter (%L. Pm), Mineral apposition rate(MAR), Bone formation rate (BFR/BV) and so on reduced significantly. Percent trabecular area (%Tb. Ar) and Trabecular number (Tb. N) were obviously higher while Trabecular separation (Tb. sp) was remarkablely lower than those of the control group. BMD in Dex-L and the content of hydroxyproline in Dex-M reduced notablely. Biomechanical property of Dex groups decreased significantly. Dex suppressed bone formation and reduced bone turnover significantly. As the increase doses of Dex, %Tb. Ar increased, and, on the contrary, BMD and biomechanical property decreased with the reduced matrix in bone at the same time. It suggested that non-mineralized bone formation increased and biomechanical property deceased. The doses of 1 mg/kg Dex had the most obvious effect on bone quality. This dose slightly increased %Tb. Ar, however, bone formation, bone biomechanical property and matrix in bone decreased obviously. Diffferent doses of Dex have different effects on bone qualities. However the dose has no direct influcing ratio to the bone qualities.
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Animals , Female , Rats , Bone Density , Dexamethasone , Pharmacology , Dose-Response Relationship, Drug , Osteoporosis , Pathology , Random Allocation , Rats, Sprague-Dawley , Tibia , Metabolism , PathologyABSTRACT
This investigation was directed to the effects of DanShenGuBao on biomechanical properties and bone mineral density (BMD) of femur induced by retinoic acid (RA) in rats. Forty 4-month-old virgin female Sprague-Dawley rats were randomly divided into 5 groups(8 rats each) control group, RA group and different doses of DanShenGuBao groups. Rats in control group were given vehicle, rats in other four groups were given RA at 70 mg x kg(-1) x d(-1) in the morning and given different drugs in the afternoon at the same time. Rats in RA group were given vehicle, rats in other groups were given different doses of DanShenGuBao which contained 10 mg x kg(-1) x d(-1), 5 mg x kg(-1) x d(-1), 2.5 mg x kg(-1) x d(-1) tanshinol, respectively. All of rats were treated at 5 ml x kg(-1) by oral gavaged for 28 days. In preparation for the determination of dynamic changes in bone tissues, all rats were given subcutaneous injections of 30 mg x kg(-1) tetracycline on the 14th, 13th day and 5 mg x kg(-1) calcein on the 4th, 3rd day before death. At the experimental endpoint, the rats were sacrificed by cardiac puncture under sodium pentobarbital anesthesia. Physical parameters, BMD and biomechanical properties of femur were assessed. Compared with those in control group, the physical parameters (cross-sectional diameter, wet and dry weight), BMD and biomechanical properties (max-load, elasticity-load, break-strain, rigid coefficient and bending-energe) were significantly decreased in RA group. Compared with that in RA group, the BMD of femur was increased significantly in medium and high dose of DanShenGuBao group, but there was no significant change in physical parameters and biomechanical properties of femur. RA could decrease the physical parameters, BMD and biomechanical properties of femur. DanShenGuBao could increase BMD, but it was found with no obvious effect on physical parameters and biomechanical properties.
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Animals , Female , Rats , Absorptiometry, Photon , Biomechanical Phenomena , Bone Density , Drugs, Chinese Herbal , Therapeutic Uses , Femur , Diagnostic Imaging , Osteoporosis , Drug Therapy , Phytotherapy , Random Allocation , Rats, Sprague-Dawley , Salvia miltiorrhiza , Chemistry , TretinoinABSTRACT
Aim To investigate the effects of retinoic acid (RA) on induction osteroporosis model rats andpreventive effects of Danshengubao.Methods 4-month-old female Sprague-Dawley rats were given RA at 70 mg·kg~(-1)·d~(-1) and were given Danshengubao at different doses at the same time.All rats were treated by oral gavaged for 28 days.The static and dynamic parameters in cancellous bone of the fifth lumbar vertebrae (LV5) were examined and the dynamic changes of the tibial shaft (Tx) were observed with histomorphometrical analyses; the forth lumbar vertebrae (LV4) was used to perform the compression test.Results Compared with control group, biomechanical properties of LV4, the static parameters ( total tissue area, trabecular area, trabecular perimeter) and the dynamic parameters of LV5 were significantly decreased in RA group.Compared with control group, bone formation of Tx was decreased in periosteal surfaces but enhanced in endocortical surfaces in RA group.Compared with RA group, the biomechanical properties of LV4 were increased significantly in low and medium dose of Danshengubao groups.Conclusion sRA can decrease the size and the biomechanical properties of LV, but it can not change the percentage trabecular area. The mechanism may be related to the act that RA can inhibit cancellous bone formation, decrease the modeling of cortical bone in periosteal surfaces and enhance the remolding of cortical bone in endocortical surfaces. Danshengubao can improve biomechanics of LV induced by RA in rats.
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BACKGROUND:Disequilibrium of proportion of adipogenesis and osteogenesis from bone marrow mesenchymal stem cells (BMSCs)is associated with many bone diseases.However,it has been demonstrated that Wnt signaling pathway could play an important role in regulation of BMSC differentiation.OBJECTIVE:To investigate the different gene expression profiles and to find the target gene on Wnt signaling pathway of the BMSCs,after being induced to osteoblasts and adipocytes respectively using Wnt signaling pathway PCR array.METHODS:The third-passage BMSCs,after being induced to osteoblasts and adipocytes respectively for 7 days.The total mRNA of MSCs was extracted by Trizol.BMSC morphology was observed following osteogenic and adipogenic induction under an inverted microscope.Gene array was detected by rat Wnt signaling pathway PCR array.Non-induction group served as controls.The ratio of increase/reduction gene of osteoblasts and adipocytes was calculated.RESULTS AND CONCLUSION:Under an inverted microscope,BMSCs with high homogenicity were obtained following passage 3.BMSCs differentiated into osteoblasts following osteogenic induction,and into adipocytes following adipogenic induction.Compared with non-induction group,fifteen genes(Dkk1,kremen,FZD1,FZD7,et al.)were expressed up-regulated(ratio ＞ 2)and 16(sFrp 5,β-catenin,Dvl3,Tcf7,et al.)genes down-regulated(ratio ＜ 0.5)when the third-passage BMSCs were induced to adipocytes.Six genes(Dkk1,kremen,β-catenin,Wnt11,et al.)were expressed up-regulated and 15 genes(sFrp5,sFRP4,Fzd1,et al.)down-regulated when BMSCs being induced to osteoblasts.Above-mentioned results suggested that Wnt signaling pathway plays an important role in the osteoblast and adipocyte differentiation from BMSCs.
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<p><b>OBJECTIVE</b>To investigate the effect of tanshinone IIA (TanIIA) on the expression of tissue factor (TF) and matrix metalloproteinase-12 (MMP-12) in RAW264.7 cells and explore the possible mechanism.</p><p><b>METHODS</b>RAW 264.7 cells were incubated with ox-LDL in the presence or absence of different concentrations of tanshinone IIA. At the end of the incubation, the cell proliferation was assessed by MTT assay, and superoxide dismutase (SOD) activity and malondialdehyde (MDA) and TF concentrations in the supernatant were detected by xanthine oxidase method, thiobarbituric acid method and ELISA, respectively. Western blotting was employed to determine MMP-12 expression in the cells.</p><p><b>RESULTS</b>The cell proliferation was dose-dependently inhibited by TanIIA. SOD activity in the supernatant was increased significantly, while the MDA and TF concentration and MMP-12 expression in cells decreased after treatment of the cells with different concentrations of TanIIA.</p><p><b>CONCLUSION</b>TanIIA inhibits the cell proliferation and TF and MMP-12 expressions in RAW264.7 cells stimulated by ox-LDL, and these effects may be related with the anti-oxidation property of TanIIA.</p>