scholarly journals Lentivirus-TAZ Administration Alleviates Osteoporotic Phenotypes in the Femoral Neck of Ovariectomized Rats

2016 ◽  
Vol 38 (1) ◽  
pp. 283-294 ◽  
Author(s):  
Zhanhai Yin ◽  
Yan Zhang ◽  
Zheyang Wang ◽  
Lin Ding ◽  
Ainiwaerjiang Damaolar ◽  
...  

Background: Osteoporosis is characterized by impairment of bone mass, strength, and microarchitecture, leading to the susceptibility to fragility fractures, especially in femoral neck region. Transcriptional coactivator with PDZ-binding motif (TAZ) facilitates osteogenesis while suppressing adipogenesis via regulation of transcriptional activities of runt-related transcription factor 2 and peroxisome proliferator-activated receptor γ. Here, we validated the role of TAZ in vivo using an ovariectomized (OVX) rat model of osteoporosis. Methods: Serum alkaline phosphatase, triglyceride, cholesterol and urinary hydroxyproline were measured on an automatic analyzer using diagnostic reagent kits. Serum OCN and C-terminal cross-linked telopeptides of type I collagen were measured using ELISA. Bone mineral density was measured using dual-energy X-ray scanner. Mechanical parameters were detected by three-point bending assays. Bone volume per tissue volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. No), and trabecular separation (Tb. Sp) were measured by MicroCT. The mRNA and protein levels were quantified by Realtime PCR and Western Blotting respectively. Results: After injections of lentivirus overexpressing TAZ into the femoral neck region, bone mineral density, ultimate force, stiffness, BV/TV, Tb. Th, and Tb. No were significantly increased, whereas Tb. Sp was dramatically decreased. In the TAZ-overexpression region in the femoral neck of OVX rats, the mRNA levels of Runx2 and osteocalcin were obviously elevated, whereas that of PPARγ and adipocyte protein 2 were downregulated. Conclusion: Lentivirus-mediated TAZ gene therapy alleviated the osteoporotic phenotypes in the femoral neck of OVX rats, providing an alternative strategy for the treatment of postmenopausal osteoporosis and prevention of osteoporotic fracture.

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Yasumoto Matsui ◽  
Marie Takemura ◽  
Atsushi Harada ◽  
Fujiko Ando ◽  
Hiroshi Shimokata

Bone mineral density (aBMD) is equivalent to bone mineral content (BMC) divided by area. We rechecked the significance of aBMD changes in aging by examining BMC and area separately. Subjects were 1167 community-dwelling Japanese men and women, aged 40–79 years. ABMDs of femoral neck and lumbar spine were assessed by DXA twice, at 6-year intervals. The change rates of BMC and area, as well as aBMD, were calculated and described separately by the age stratum and by sex. In the femoral neck region, aBMDs were significantly decreased in all age strata by an increase in area as well as BMC loss in the same pattern in both sexes. In the lumbar spine region, aBMDs decreased until the age of 60 in women, caused by the significant BMC decrease accompanying the small area change. Very differently in men, aBMDs increased after their 50s due to BMC increase, accompanied by an area increase. Separate analyses of BMC and area change revealed that the significance of aBMD changes in aging was very divergent among sites and between sexes. This may explain in part the dissociation of aBMD change and bone strength, suggesting that we should be more cautious when interpreting the meaning of aBMD change.


2001 ◽  
Vol 86 (4) ◽  
pp. 521-527 ◽  
Author(s):  
Joseé Gala ◽  
Manuel Di´az-curiel ◽  
Concepcioó de la Piedra ◽  
Jesu´s Calero

At the level of prevention of bone mineral loss produced by ovariectomy, the aim of the present study was to determine the effect produced by supplementation of Ca in the diet and a moderate exercise programme (treadmill), simultaneously or separately, in ovariectomized rats, an experimental model of postmenopausal bone loss. Female Wistar rats (n110, 15 weeks old) were divided into five groups: (1) OVX, rats ovariectomized at 15 weeks of age, fed a standard diet; (2) SHAM, rats sham operated at 15 weeks of age, fed a standard diet; (3) OVX–EX, ovariectomized rats, fed a standard diet and performing the established exercise programme; (4) OVX–Ca, ovariectomized rats fed a diet supplemented with Ca; (5) OVX–EXCa, ovariectomized rats with the exercise programme and diet supplemented with Ca. The different treatments were initiated 1 week after ovariectomy and were continued for 13 weeks for subgroup 1 and 28 weeks for subgroup 2, to look at the interaction of age and time passed from ovariectomy on the treatments. Bone mineral density (BMD) was determined, at the end of the study, in the lumbar spine (L2, L3 and L4) and in the left femur using a densitometer. Bone turnover was also estimated at the end of the study, measuring the serum formation marker total alkaline phosphatase (AP) and the resorption marker serum tartrate-resistant acid phosphatase (TRAP). As expected, OVX rats showed a significant decrease (P<0·05) in BMD, more pronounced in subgroup 2, and a significant increase in AP and TRAP with regard to their respective SHAM group. The simultaneous treatment with Ca and exercise produced the best effects on lumbar and femoral BMD of ovariectomized rats, partially avoiding bone loss produced by ovariectomy, although it was not able to fully maintain BMD levels of intact animals. This combined treatment produced a significant increase in AP, both in subgroups 1 and 2, and a decrease in TRAP in subgroup 1, with regard to OVX group. The exercise treatment alone was able to produce an increase in BMD with regard to OVX group only in subgroup 1 of rats (younger animals and less time from ovariectomy), but not in subgroup 2. In agreement with this, there was an increase of AP in both subgroups, lower than that observed in animals submitted to exercise plus Ca supplement, and a decrease of TRAP in subgroup 1, without significant changes in this marker in the older rats. Ca treatment did not produce any significant effect on BMD in OVX rats in both subgroups of animals, showing a decrease of AP and TRAP levels in the younger animals with no significant variations in markers of bone remodelling in the older female rats compared with their respective OVX group.


2015 ◽  
Vol 42 (8) ◽  
pp. 1413-1417 ◽  
Author(s):  
Haibo Li ◽  
Qiuxia Li ◽  
Xi Chen ◽  
Chen Ji ◽  
Jieruo Gu

Objective.To evaluate the effect of anti-tumor necrosis factor (TNF) therapy on bone mineral density (BMD) in patients with active ankylosing spondylitis (AS) with low BMD.Methods.Eighty-nine patients with active AS with low BMD were randomly divided into either a study group or a control group. The study group received etanercept (50 mg/week) or adalimumab (40 mg/2 week) subcutaneously for 1 year. BMD of lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry, and bone turnover markers serum C telopeptide of type-I collagen (sCTX) and serum procollagen type-I N propeptide (PINP) were detected by ELISA at baseline and at end of study.Results.After 1 year, compared with baseline, there was a significant increase in spine and femoral neck BMD by a mean ± SD of 14.9% ± 15.6% (p < 0.0001) and 4.7% ± 7.9% (p < 0.0001) in the study group. In the control group, there was a significant decrease in spine and femoral neck BMD by a mean ± SD of −8.6% ± 9.7% (p < 0.0001) and −9.8% ± 11.5% (p < 0.0001). Compared with baseline, sCTX was significantly decreased in the study group (−40% at 1 yr, p < 0.0001), but bone-specific alkaline phosphatase and PINP increased (45.6%, p < 0.0001 and 30.8%, p < 0.0001, respectively).Conclusion.In patients with active AS with low BMD, the spine and femoral neck BMD increased after anti-TNF therapy for 1 year, and it was accompanied by a significant decrease in bone resorption markers and an increase in bone formation markers.


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Ágnes Horváth ◽  
Edit Végh ◽  
Anita Pusztai ◽  
Zsófia Pethő ◽  
Attila Hamar ◽  
...  

Abstract Objective We wished to determine bone alterations in systemic sclerosis (SSc) patients by conventional densitometry (DXA), peripheral quantitative computed tomography (pQCT), and bone biomarkers. Methods We included 44 SSc patients and 33 age-matched healthy controls. Lumbar spine and femoral neck bone mineral density (BMD) was assessed by DXA. Volumetric BMD was measured by pQCT at the radius. FRAX, 25-hydroxyvitamin-D3 (25-OH-D3), parathyroid hormone, osteocalcin, C-terminal collagen telopeptide, and procollagen type I amino-terminal propeptide were also assessed. Results SSc patients had lower L2–4 BMD (0.880 ± 0.108 vs. 0.996 ± 0.181 g/cm2; p = 0.019) and femoral neck (FN) BMD (0.786 ± 0.134 vs. 0.910 ± 0.090 g/cm2; p = 0.007) by DXA. In SSc vs. controls, pQCT indicated lower mean cortical (328.03 ± 103.32 vs. 487.06 ± 42.45 mg/cm3; p < 0.001) and trabecular density (150.93 ± 61.91 vs. 184.76 ± 33.03 mg/cm3; p = 0.037). Vitamin D3 deficiency was more common in SSc vs. controls (60.0% vs. 39.3%; p = 0.003). L2–4 (p = 0.002) and FN BMD (p = 0.015) positively correlated with BMI. pQCT assessments confirmed an inverse correlation between pulmonary manifestation and total (p = 0.024), trabecular (p = 0.035), and cortical density (p = 0.015). Anti-Scl70 positivity inversely correlated with pQCT total density (p = 0.015) and the presence of digital ulcers with cortical density (p = 0.001). We also found that vertebral and FN BMD as determined by DXA significantly correlated with pQCT total, trabecular, and cortical density (p < 0.05). Conclusion The results of our study suggest that bone loss in SSc patients may be associated with lower BMI, anti-Scl70 positivity, and the presence of pulmonary manifestations and digital ulcers. Both DXA and pQCT are appropriate tools to evaluate the bone alterations in SSc patients.


2021 ◽  
Vol 20 (2) ◽  
pp. 247-252
Author(s):  
Ruran Wang ◽  
Yanhua Feng ◽  
Shengnan Huang ◽  
Yujie Zhang ◽  
Meijie Liu ◽  
...  

Traditional Chinese medicine recommends kidney-tonifying treatment for osteoporosis. Zuogui pill is one such treatment composed of eight well characterized Chinese medicinal herbs (Radix rehmanniae preparata, Fructus lycii, Rhizoma dioscoreae, F. corni, Semen cuscutae, Colla cornus cervi, C. carapacis et Plastri testudinis, and R. achyranthis bidentatae). The aim of the study is to evaluate the effects of the Zuogui pill on osteoporosis in ovariectomized rats and to identify the signaling pathways that mediate its action on the bones. A total of 46 6-month-old female Sprague-Dawley rats were divided into four groups: sham-operated control, bilaterally ovariectomized, ovariectomized rats receiving diethylstilbestrol (the positive control group), and ovariectomized rats receiving the Zuogui pill. By the end of 8-week treatments, the following parameters were assessed: (a) bone mineral density and trabecular histomorphology, (b) the expression levels of receptor activator of nuclear factor kappa B ligand and osteoprotegerin in rat tibial osteoblasts and (c) bone marrow stromal cells. The Zuogui pill treatment elevated the trabecular bone area and trabecular thickness and reduced the trabecular spacing in rats with ovariectomy-induced osteoporosis. Compared to the ovariectomized group, the Zuogui pill treatment significantly increased the levels of bone mineral density and osteoprotegerin and suppressed the level of receptor activator of the nuclear factor kappa B ligand. These data led us to conclude that the Zuogui pill regulates bone metabolism and improves osteoporosis symptoms possibly through the osteoprotegerin/receptor activator of the nuclear factor kappa B ligand/receptor activator of the nuclear factor kappa B signaling pathway.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Hongmei Mao ◽  
Wenjun Wang ◽  
Lili Shi ◽  
Chen Chen ◽  
Chao Han ◽  
...  

Abstract Background Data from the 2010–2012 Chinese National Nutrition and Health Survey showed that the vast majority of postmenopausal women in China had dual deficiencies in calcium and estrogen. Objective This study aimed to clarify whether calcium supplementation alleviated bone loss caused by calcium restriction combined with estrogen deficiency in rats. Methods Forty-eight female rats aged 9 weeks were assigned to 4 groups and fed a low-calcium diet: sham-operated (SHAM-LC), ovariectomized (OVX-LC), and ovariectomized rats treated with 750 mg/kg (OVX-LC-M) or 2800 mg/kg CaCO3 (OVX-LC-H). CaCO3 or distilled water was administered orally for 13 weeks. Bone mineral density (BMD) and histomorphometry of the femur, serum biochemical parameters, and serum metabolites were analyzed. Results The OVX-LC rats showed a significant increase in body weight and serum levels of lipid markers, a significant decrease in serum estradiol, calcium, phosphorus, and 25(OH)D levels, and deterioration of the femur. At 750 mg/kg and 2800 mg/kg, CaCO3 reduced the deterioration of trabecular bone and increased the trabecular area percentage (Tb.Ar %) and BMD of the femur. Serum estradiol levels increased in a dose-dependent manner after CaCO3 supplementation (p < 0.01). The administration of 2800 mg/kg CaCO3 decreased serum triglyceride and high-density lipoprotein levels (p < 0.05) and decreased the levels of the bone turnover markers osteocalcin, N-telopeptide of type I collagen and β-crosslaps. The results of the metabolomics analysis showed that the glycerophospholipid metabolism pathway was closely related to calcium supplementation, and more DG (44:6 n3), LysoPC (22:2) and PE (P-34:3) and less Cer (d43:0) and PE-NMe2 (46:3) were produced. Conclusions The results clearly indicated that calcium supplementation was beneficial for decreasing bone loss in OVX-LC rats. The present study is the first to show that calcium supplementation increased the estradiol content in OVX-LC rats, and the effect of calcium on bone loss may be partially attributed to the increase in the estrogen level that subsequently induced the changes in metabolite levels, eventually increasing the bone mineral density to a relatively higher level to reduce bone deterioration.


Author(s):  
Ángel Matute-Llorente ◽  
Alejandro González-Agüero ◽  
Germán Vicente-Rodríguez ◽  
Luís B. Sardinha ◽  
Fátima Baptista ◽  
...  

AbstractBackground:Low bone mineral density (BMD) has been frequently described in subjects with Down syndrome (DS). Reduced physical activity (PA) levels may contribute to low BMD in this population. The objective of the study was to investigate whether PA levels were related to the femoral neck bone mass distribution in a sample of 14 males and 12 females with DS aged 12–18 years.Methods:BMD was evaluated by dual energy X-ray absorptiometry (DXA) at the integral, superolateral and inferomedial femoral neck regions and PA levels were assessed by accelerometry. The BMDs between the sexes and PA groups (below and above the 50th percentile of the total PA) were compared using independent t-tests and analyses of covariance (ANCOVAs) controlling for age, height and body weight.Results:No differences were found between the BMDs of males and females in any femoral neck region (p>0.05). Females with higher PA levels demonstrated increased integral (0.774 g/cmConclusions:This investigation shows that females accumulating more total PA presented increased BMDs at the integral and superolateral femoral neck regions (14.1% and 17.0%, respectively) when compared to their less active peers. These data highlight the importance of PA in females with DS to counteract their low bone mass and to improve their bone health.


Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 1767-1778 ◽  
Author(s):  
Yanfei L. Ma ◽  
Qing Q. Zeng ◽  
Leah L. Porras ◽  
Anita Harvey ◽  
Terry L. Moore ◽  
...  

We compared teriparatide (TPTD) and strontium ranelate (SR) efficacy on bone formation activity in a mature rat model of estrogen-deficiency bone loss. Rats were ovariectomized (OVX) at age 6 months and permitted to lose bone for 2 months to establish osteopenia before initiation of treatment with TPTD (5 or 15 μg/kg · d sc) or SR (150 or 450 mg/kg · d oral gavage). After 3 wk, RT-PCR analyses of bone formation genes in the distal femur metaphysis showed significant elevation of collagen 1α2, osteocalcin, bone sialoprotein, alkaline phosphatase, and Runx2 gene expression at both TPTD doses, relative to OVX controls. SR had no significant effect on expression of these genes. TPTD treatment for 12 wk dose dependently increased lumbar vertebral (LV) and femoral midshaft bone mineral content (BMC) and bone mineral density over pretreatment and age-matched OVX controls. SR 150 increased BMC, and SR 450 increased BMC and bone mineral density of femoral midshaft and LV over OVX controls. There were significant dose-dependent TPTD increases of LV and femoral neck strength, and TPTD 15 also increased midshaft strength compared with pretreatment and age-matched OVX controls. SR did not enhance bone strength relative to pretreatment or age-matched OVX controls. Histomorphometry of the proximal tibial metaphysis showed dose-dependent effects of TPTD on trabecular area, number, width, and osteoblast surface, bone mineralizing surface, and bone formation rate relative to pretreatment and age-matched OVX controls, whereas SR had no effect on these parameters. These findings confirmed the bone anabolic efficacy of teriparatide, but not SR in mature, osteopenic, OVX rats.


2007 ◽  
Vol 35 (04) ◽  
pp. 669-680 ◽  
Author(s):  
Meng-Hsiun Tsai ◽  
G. Steven Huang ◽  
Yao-Ching Hung ◽  
Liu Bin ◽  
Lung-Te Liao ◽  
...  

We evaluated the protective effect of Psoralea corylifolia L. (PCL) extract on the ovariectomized (OVX) rat model. The biochemical markers of bone turnover, calcium metabolism, and calcium balance were examined. PCL extract (25 mg or 50 mg/kg body weight/day) was orally administrated to OVX rats for 3 months. PCL extract did not alter weight gain or uterus weight in OVX rats. PCL extract significantly increased serum Ca (calcium) levels ( p < 0.05, vs. OVX group) as well as decreased urinary Ca excretion ( p < 0.05 vs. OVX group) in OVX rats. The upregulation of serum osteocalcin level by ovariectomy was suppressed by treatment with PCL extract in rats ( p < 0.05, vs. OVX group). PCL extract increased bone mineral density at 50 mg/kg body weight/day in OVX rats ( p < 0.05, vs. OVX group). Our results indicate that orally administrated PCL extract can decrease urinary calcium excretion and decrease serum osteocalcin in OVX rats, resulting in positive effects on bone mineral density as well as bone formation. In conclusion, our studies showed that PCL might be a potential candidate for treatment of postmenopausal osteoporosis.


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