OBJECTIVESTo investigate the mechanism of Liuwei Dihuang Pill (, LDP) in treating postmenopausal osteoporosis (PMOP) with Shen (Kidney) yin deficiency.

METHODSIn this study, 205 cases of PMOP were divided into the PMOP Shen-yin deficiency group (Group A), PMOP Shen-yang deficiency group (Group B), PMOP without Shen deficiency group (Group C), and control group (Group N). Real-time polymerase chain reaction (RT-PCR) and Western blot techniques were used to observe the effects of LDP treatment on the cardiotrophin-like cytokine factor 1 (CLCF1), ankyrin repeat and SOCS box containing 1 (ASB1), and prokineticin 2 (PROK2) genes and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway.

RESULTSThe mRNA (P<0.05) and protein (P<0.01) expression levels of the CLCF1 gene in Group A were significantly lower than the corresponding levels in Group N. After LDP treatment for 3 months, the mRNA expression levels of the CLCF1 gene were obviously up-regulated (P<0.01). After 6-month treatment, the expression levels of CLCF1 mRNA and protein were significantly up-regulated (both P<0.01), and the average bone density of the top femur had significantly increased (P<0.05). In vitro, CLCF1 overexpression resulted in a significant increase in the total protein and phosphorylated protein levels of JAK2 and STAT3.

CONCLUSIONSThe CLCF1 gene is an important gene associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gene expression and activation of the JAK/STAT signaling pathway.

Cytokines ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gene Expression Regulation ; Humans ; Janus Kinases ; metabolism ; Middle Aged ; Osteoporosis, Postmenopausal ; drug therapy ; genetics ; RNA, Messenger ; genetics ; metabolism ; STAT Transcription Factors ; metabolism ; Signal Transduction ; Up-Regulation ; Yin Deficiency ; drug therapy ; genetics

OBJECTIVETo observe the impact of bone morphogenetic protein-2 (rhBMP-2) on bone marrow stromal cells (BMSCs) osteogenesis in vitro and vascular endothelial growth factors (VEGF) expression in bone osteoporotic to prevent and treat the osteoporosis.

METHODSTwenty 6-month-old female SD rats weighted (300±20) g underwent bilateral ovariectomized. At 3 months after operation, dual-energy X-ray absorptiometry was used to measure bone mineral density of rats,the values were compared with preoperative to ensure the model successfully, and the osteoporosis rats' BMSCs were cultured by bone marrow adherent cultured and the BMSCs morphology was observed under a phase contrast microscope upside down. The osteoporosis rats' BMSCs at the 2nd generation (p2) were randomly divided into experimental and control groups and were added complete medium (containing rhBMP-2) and osteogenic induced liquid, respectively. Two weeks later, the formation of cell calcium nodules were detected by Alizarin red staining method,alkaline phosphatase activity was measured by enzyme standard instrument and the expression of VEGF was detected by RT-PCT method.

RESULTS(1)Whole body bone mineral density of rats before and after operation were (0.179±0.007), (0.158±0.006) g/cm2,there was statistically significant (t=4.180,P< 0.05). (2)Alizarin red staining at 2 weeks after osteogenesis induced by BMSCs (P2) in the experimental group had more strong dyeing effect than the control group obviously. (3)Alkaline phosphatase activity at 2 weeks after osteogenesis induced by BMSCs (P2) of the experimental group (15.62±1.27) ug/gprot was significantly higher than that of the control group (8.62±0.93) ug/gprot,there was statistically significant (t=7.709, P<0.01). (4)The expression of VEGF at 2 weeks after osteogenesis induced by BMSCs (P2) of the experimental group 3.723±0.143 was significantly higher than that of the control group 0.950±0.072, there was statistically significant (t=29.462, P<0.01).

CONCLUSIONRhBMP-2 can improve the in-vitro osteogenesis ability of ovary osteoporosis rat BMSCs, promote the VEGF expression of osteogenesis factor. Regulating the VEGF expression may be one of the mechanisms of BMP-2 to participate in bone metabolism.

Animals ; Bone Density ; Bone Morphogenetic Protein 2 ; genetics ; metabolism ; Cells, Cultured ; Female ; Humans ; In Vitro Techniques ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Osteogenesis ; Osteoporosis, Postmenopausal ; genetics ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVETo study the effect of eight specifications of Cervi Cornu Pantotrichum on the osteoporosis of ovariectomized rats and grade the eight different specifications of Cervi Cornu Pantotrichum.

METHODTotally 100 SD female rats were divided randomly into 10 groups, namely the normal group, the model group and eight Cervi Cornu Pantotrichum groups of different specifications. Their bilateral ovaries were excised to reproduce the osteoporosis model. Meanwhile, the rats were given the eight different specifications of Cervi Cornu Pantotrichum for consecutively 12 weeks. Subsequently, the effects of the different specifications of Cervi Cornu Pantotrichum on bone mineral density and serum biochemical indicators of rats were observed. A clustering analysis was made for the eight specifications of Cervi Cornu Pantotrichum, with the serum content of ALP, BMP-2 and BGP as influencing factors.

RESULTAfter 12 weeks, the eight different specifications of Cervi Cornu Pantotrichum could significantly improve ALP, BMP-2, BGP in serum and bone mineral density of ovariectomized rats. And the cluster analysis showed similar results to the quality classification of traditional commercial herbs Cervi Cornu Pantotrichum.

CONCLUSIONDifferent specifications of Cervi Cornu Pantotrichum can antagonize the osteoporosis of ovariectomized rats, and their effects are related to the quality of commercial herbs.

Animals ; Bone Density ; drug effects ; Bone Morphogenetic Protein 2 ; genetics ; metabolism ; Deer ; Disease Models, Animal ; Female ; Horns ; chemistry ; Humans ; Osteoporosis, Postmenopausal ; drug therapy ; genetics ; metabolism ; physiopathology ; Ovariectomy ; Rats ; Rats, Sprague-Dawley

BACKGROUNDGenetic factors are important in the pathogenesis of osteoporosis, but less is known about the genetic determinants of osteoporosis treatment. We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase (FDPS) in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China.

METHODSThe study group comprised 639 postmenopausal women aged (62.2 ± 7.0) years with osteoporosis or osteopenia who had been randomly assigned to low dose group (70 mg/2 w) or standard dose group (70 mg/w) of alendronate in this 1-year study. We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul. Before and after treatment, serum levels of calcium, phosphate, alkaline phosphatase (ALP), cross linked C-telopeptide of type I collagen (β-CTX) were detected. Bone mineral density (BMD) at lumbar spine and proximal femur was measured. The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD, bone turnover biomarkers after the treatment.

RESULTSThe FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck, and patients with CC genotype had significantly higher baseline femoral neck BMD ((733.6 ± 84.1) mg/cm(2)) than those with AC genotypes ((703.0 ± 86.9) mg/cm(2)) and AA genotypes ((649.8 ± 62.4) mg/cm(2)) (P < 0.01). No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS. The percentage change of serum ALP level was significantly lower in patients with CC genotype (-22.9%) than that in those with AC genotype (-24.1%) and AA genotype (-29.8%) of FDPS after 12 months of alendronate treatment (P < 0.05). Neither percentage change of BMD nor β-CTX level after alendronate treatment had association with FDPS genotype.

CONCLUSIONSFDPS gene was probably a candidate gene to predict femoral neck BMD at baseline. FDPS gene alleles could predict change percentage of ALP after treatment of alendronate, but possibly had no significant relationship with the responsiveness of BMD to alendronate therapy.

Alendronate ; therapeutic use ; Asian Continental Ancestry Group ; Bone Density Conservation Agents ; therapeutic use ; Female ; Geranyltranstransferase ; genetics ; Humans ; Middle Aged ; Osteoporosis, Postmenopausal ; drug therapy ; genetics ; Polymorphism, Genetic

To propose the new concept of multidimensional omics, and define that the multidimensional omics is a proper method for studying the material base and mechanism of traditional Chinese medicine (TCM) compounds. Zhuanggu Zhitong capsule was taken for example to study its effect against experimental postmenopausal osteoporosis. From the perspective of chemi-omics, genomics and proteomics of TCM, it systematically interpreted the efficacious materials and mechanisms of Zhuanggu Zhitong capsule in preventing and treating experimental postmenopausal osteoporosis, while taking the lead in designing a three dimensional form to intuitively exhibit the results of the multidimensional omics study. This study provides a new idea and solution for studies on the efficacious materials and mechanisms of TCM compounds.
Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Female ; Gene Expression ; drug effects ; Genomics ; Humans ; Osteoporosis, Postmenopausal ; drug therapy ; genetics ; metabolism ; Proteomics

OBJECTIVETo observe the effect of treadmill exercise on the mRNA expression of osteoprotegerin, RANKL and RUNX2 in bone tissue of ovariectomized rat,and to investigate the mechanism of treadmill exercise for the preventing and treating postmenopausal osteoporosis.

METHODSThirty healthy adult SD rats which average weight was (270 +/- 10) g were randomly divided into 3 groups: sham-operation group, ovariectomized group and treadmill exercise group. Each group had 10 rats. After anesthesia, ovariectomized group and treadmill exercise treated group were operated by bilateral ovarian resection, sham group by sham operation. Sham-operation group and ovarian rats were normal breed. Rats in the exercise group were treated by running on treadmill for animal at 1 week after the operation. Running speed was 18 meters per minutes lasting 45 minutes in one day, and worked six days per week for 11 weeks. All rats were killed after 12 weeks. After decalcification, left femur head was made to paraffin slice and observed by inverted phase contrast microscope for histological examination. Total RNA were extracted from the right femur heads and the mRNA expression of OPG,RANKL and RUNX2 were examined by real time PCR.

RESULTSThe femur heads of ovariectomized group showed thin trabecular bone and less bone cells, meanwhile trabecular bone of exercise group looked thicker in histological examination. The mRNA expression of OPG (0.131 +/- 0.080), RANKL (8.013 +/- 3.550) and RUNX2 (3.245 +/- 5.090) was seen in the ovariectomized group. Meanwhile different results were found as the mRNA expression of OPG (0.566 +/- 0.260), RANKL (5.232 +/- 3.670) and RUNX2 (2.753 +/- 3.680) in the group of treadmill exercise. In compared with ovariectomized group, the mRNA expression of OPG in treadmill exercise increased and the result had statistical significance,whereas mRNA expression of RNAKL and RUNX2 decreased but the results had no statistical significance.

CONCLUSIONThe effect of exercise treating postmenopausal osteoporosis is tightly correlated with the up-regulation of expression of OPG. This provides a new train of thought of postmenopausal osteoporosis treatment for the future study.

Adult ; Animals ; Bone Density ; Core Binding Factor Alpha 1 Subunit ; genetics ; metabolism ; Exercise Test ; Exercise Therapy ; Female ; Femur ; metabolism ; Humans ; Osteoporosis, Postmenopausal ; genetics ; metabolism ; physiopathology ; therapy ; Osteoprotegerin ; genetics ; metabolism ; Ovariectomy ; RANK Ligand ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley

Adiponectin may affect bone through interactions with two known receptors, adiponectin receptors (ADIPOR) 1 and 2. We examined the association between polymorphisms of ADIPOR1 and ADIPOR2 and bone mineral density (BMD) in postmenopausal Korean women. Six polymorphisms in ADIPOR1 and four polymorphisms in ADIPOR2 were selected and genotyped in all study participants (n = 1,329). BMD at the lumbar spine and femur neck were measured using dual-energy X-ray absorptiometry. Lateral thoracolumbar (T4-L4) radiographs were obtained for vertebral fracture assessment and the occurrence of non-vertebral fractures examined using self-reported data. P values were adjusted for multiple testing using Bonferroni correction (Pcorr). ADIPOR1 rs16850799 and rs34010966 polymorphisms were significantly associated with femur neck BMD (Pcorr = 0.036 in the dominant model; Pcorr = 0.024 and Pcorr = 0.006 in the additive and dominant models, respectively). Subjects with the rare allele of each polymorphism had lower BMD, and association of rs34010966 with BMD showed a gene dosage effect. However, ADIPOR2 single nucleotide polymorphisms and haplotypes were not associated with BMD at any site. Our results suggest that ADIPOR1 polymorphisms present a useful genetic marker for BMD in postmenopausal Korean women.
Base Sequence ; Bone Density/*genetics ; Female ; Femur Neck/physiology ; Genetic Association Studies ; Genetic Markers ; Genetic Predisposition to Disease ; Genotype ; Humans ; Osteoporosis, Postmenopausal/*genetics ; Polymorphism, Single Nucleotide ; Postmenopause ; Receptors, Adiponectin/*genetics ; Republic of Korea ; Sequence Analysis, DNA

BACKGROUNDA number of studies have examined the association between estrogen receptor alpha (ESR-α) gene polymorphisms and bone mineral density (BMD), but previous studies of ESR-α gene XbaI (rs9340799) and PvuII (rs2234693) polymorphisms have been hampered by small sample size, regional restrictions and inconclusive results. Thus a meta-analysis is needed to assess their pooled effects.

METHODSThis study reviewed all published articles indexed in Pubmed using the keywords in the title or abstract. All data were extracted independently by two reviewers using a standard form, the studies were meta-analyzed and minor discrepancies were resolved by authors' discussion.

RESULTSTwenty seven eligible studies involving 8467 women and 2032 men were identified. The XbaI and PvuII polymorphisms were significantly associated with BMD of the lumbar spine. XX and PP homozygotes had a protective effect in comparison with carriers of the x and p alleles, the effects were more significant in premenopausal women or Western women. At the femoral neck, the results were different. XX served as a protective factor in postmenopausal women, Western women, Western postmenopausal women, and men, while PP was likely to serve as a risk factor in Eastern women, Eastern postmenopausal women, and men.

CONCLUSIONSThe XbaI polymorphism is correlated to BMD at diverse skeletal sites. PP had a protective role for the lumbar spine but might be a risk factor for the femoral neck.

Bone Density ; genetics ; Estrogen Receptor alpha ; genetics ; Female ; Femur Neck ; pathology ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Male ; Osteoporosis, Postmenopausal ; genetics ; Polymorphism, Genetic ; genetics

Animals ; Female ; Humans ; Integrative Medicine ; trends ; Osteoporosis, Postmenopausal ; genetics ; immunology ; therapy

OBJECTIVETo study the regulation of hypoxia inducible factor-1alpha (HIF-1alpha) on osteoblast function in postmenopausal osteoporosis.

METHODSFrom October 2004 to May 2006, Cre-Loxp recombinase was used to create mice which the HIF-1alpha gene in osteoblasts was conditional knock-out, 24 female wild-type (WT) mice and 24 female conditional knock-out (CKO) mice of 3 months old were operated on ovariotomy. At 0,4,8 weeks after operation, bone histomorphometry parameters were measured with computer image analysis in HE stain sections and in tetracycline bone double labeling fluorescence sections; Bone density and the trabecular bone architecture parameters were measured by Micro-CT; The mRNA expression of vascular endothelial growth factors (VEGF), RunX2, OC, ALP were detected with quantitative RT-PCR; The protein expression of VEGF and RunX2 were detected with Western-blotting.

RESULTSIn CKO mice, the trabecular number, volume, thickness, bone density, mineral apposition rate (MAR), the expression of VEGF, RunX2, OC, ALP on mRNA level and the expression of VEGF, RunX2 on protein level decreased significantly compared with WT mice especially in 8 weeks after operation.

CONCLUSIONSThe bone formation ability of osteoblasts in CKO mice was reduced compared with WT mice after ovariotomy. HIF-1alpha can regulate the bone formation ability of osteoblasts in postmenopausal osteoporosis.

Animals ; Blotting, Western ; Core Binding Factor Alpha 1 Subunit ; genetics ; metabolism ; Disease Models, Animal ; Female ; Femur ; metabolism ; pathology ; physiopathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Osteoblasts ; metabolism ; physiology ; Osteoporosis, Postmenopausal ; genetics ; metabolism ; physiopathology ; Ovariectomy ; Random Allocation ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism