Chronic Estradiol Administration During the Early Stage of Alzheimer's Disease Pathology Rescues Adult Hippocampal Neurogenesis and Ameliorates Cognitive Deficits in Aß1-42 Mice.

Alzheimer's disease (AD) is the leading cause of dementia and has become an important public health concern. Accumulating evidence indicates that estradiol can both facilitate and impair memory-related processes and, as a result, the precise nature of the role that estradiol plays during AD pathology remains elusive. Therefore, the present study established a mouse model of AD using stereotactic brain injection of Aß1-42 in which the mice were bilaterally ovariectomized to investigate the effects of 17ß-estradiol (E2) treatment during different stages of the AD process (early and late stages). The cognitive deficits associated with this AD model were significantly ameliorated, and there was a significant increase in hippocampal neurogenesis in Aß1-42 mice that received E2 treatment during the early stage of AD pathology. On the other hand, Aß1-42 mice that received E2 treatment during the late stage of AD pathology did not exhibit any improvements in cognitive function or hippocampal neurogenesis. To reveal the mechanisms, underlying these effects, levels of oxidative stress, activity in death-associated pathways, gliosis, and synaptic function were assessed in the hippocampus. The Aß1-42 mice that received E2 treatment during the early stage of AD pathology exhibited significant reductions in the production of nitric oxide (NO) and reactive oxygen species (ROS), a marked decrease in the activation of Cytochrome-c/Bax/Bcl-2/caspase-3 pathway, a notable decrease in the level of gliosis a significant increase in the number of synapses (ultrastructural investigation), and a marked upregulation in synaptic function-related proteins compared to mice that received E2 treatment during the late stage of AD pathology. Taken together, these findings indicate that E2 treatment during the early stage of AD pathology might be an efficient approach to ameliorate the development of this disease.

Estradiol prevents Aß 25 35-inhibited long-term potentiation induction through enhancing survival of newborn neurons in the dentate gyrus.

AIM AND METHODS: Estradiol (E2) is reported to attenuate ß-amyloid (Aß) accumulation and slow the progression of Alzheimer's disease (AD). This study explored the beneficial effect of E2 in AD using histological examination and electrophysiological recording technique in AD model mice created by intracerebroventricular injection of ß-amyloid 25-35 (Aß 25-35). RESULTS: Infusion of Aß 25-35 reduced the number of newborn neurons in the 2nd week after birth, a critical period for neurite growth, and impaired high-frequency stimulation-dependent long-term potentiation (LTP) induction in perforant path-granular synapses of hippocampal dentate gyrus (DG). Administration of E2 from the 2nd to 4th week after cell birth in Aß 25-35-mice ameliorated the impairment of newborn neurons and LTP induction in DG. Acute application of E2 failed to increase the newborn neurons and rescue LTP induction in the DG of Aß 25-35-mice. CONCLUSIONS: The effect of E2 in Aß 25-35-impaired LTP induction depends on its neuroprotection improvement.

Analysis of Thermal Field Distribution in Winter over Beijing from 1985 to 2015 Using Landsat Thermal Data.

Heat supply, automobile exhaust, industrial production and decrease of thermal inertia in winter caused by the decrease of vegetation coverage leads to an obvious difference in the distribution of the land thermal field in the winter compared with other seasons. The Urban thermal field distribution in the winter directly affects the spread of air pollutants, which has important implications for analyzing the contribution of the thermal field to particulate air pollution. Atmospheric transmissivity and atmospheric upwelling/downwelling radiance in simulations are first calculated using the moderate spectral resolution atmospheric transmittance algorithm and computer model (MODTRAN). Then, we solve the radiative transfer model of the thermal infrared band by constructing a look-up table. In addition, the accuracy estimation is performed using the simulated data, showing that when the error range of emissivity and water vapor content are confined to ±0.005 and ±0.6, respectively, the temperature retrieval error are less than 0.348 and 2.117 K, respectively indicating the high retrieval accuracy of the method. In addition, the long-term sequenced Landsat TM and ETM+ data were selected to retrieve land surface temperature (LST) during 1985-2015. The analysis of the temporal and spatial distribution of thermal fields in Beijing show that the spatial and temporal variations are observable. The spatial variation covers four levels: high temperature is distributed within the second ring, low temperature loops are distributed between the second and the fifth ring, high temperature is distributed in the outer suburb areas and the lowest temperature is distributed in the western mountainous areas. Meanwhile, the temporal variation of thermal field distribution changed a great deal during the rapid development in the past 3 decades: the low temperature loop expanded from the third to the sixth ring; the intensity and scope of the heat island effect within the second ring increased gradually.

Saponins from Aralia taibaiensis attenuate D-galactose-induced aging in rats by activating FOXO3a and Nrf2 pathways.

Reactive oxygen species (ROS) are closely related to the aging process. In our previous studies, we found that the saponins from Aralia taibaiensis have potent antioxidant activity, suggesting the potential protective activity on the aging. However, the protective effect of the saponins and the possible underlying molecular mechanism remain unknown. In the present study, we employed a D-galactose-induced aging rat model to investigate the protective effect of the saponins. We found that D-galactose treatment induced obvious aging-related changes such as the decreased thymus and spleen coefficients, the increased advanced glycation end products (AGEs) level, senescence-associated ß-galactosidase (SAß-gal) activity, and malondialdehyde (MDA) level. Further results showed that Forkhead box O3a (FOXO3a), nuclear factor-erythroid 2-related factor 2 (Nrf2), and their targeted antioxidants such as superoxide dismutase 2 (SOD2), catalase (CAT), glutathione reductase (GR), glutathione (GSH), glutamate-cysteine ligase (GCL), and heme oxygenase 1 (HO-1) were all inhibited in the aging rats induced by D-galactose treatment. Saponins supplementation showed effective protection on these changes. These results demonstrate that saponins from Aralia taibaiensis attenuate the D-galactose-induced rat aging. By activating FOXO3a and Nrf2 pathways, saponins increase their downstream multiple antioxidants expression and function, at least in part contributing to the protection on the D-galactose-induced aging in rats.

The Kunming mouse: as a model for age-related decline in female fertility in human.

To ascertain whether the Kunming (KM) mouse is an available model for age-related decline in female fertility in human or not, oocytes from young (6-8 weeks), middle-aged (9 months) and aged (12 months) female mice were compared with respect to number of oocytes, frequency of in-vitro maturation (IVM) and in-vitro fertilization (IVF), and meiotic chromosome segregation and alignment. The mean number of pups born per mouse decreased significantly from the young to the middle-aged and the aged mice. The mean number of ovarian follicles, ovarian germinal vesicle oocytes and ovulated MII oocytes decreased significantly with maternal age. The rate of IVM in oocytes from young mice (73.9%) was less significantly than that in oocytes from middle-aged and aged mice (86.1% and 84.4%, respectively). Immunocytochemical analysis showed that ageing caused a significantly higher rate (49.3%) of chromosome misalignment than that (15.7%) of the young mice. The presence of premature chromatids was also significantly higher in MII oocytes of aged mice as compared with young mice (37.8 versus 8.3%). Pronuclear formation was delayed in oocytes of middle-aged and aged females (35.5 and 42.3% respectively in 5 h of IVF) as compared with young mice (88.1%). The study suggests that KM mouse exhibits an age-related decline in female fertility. Significant reduction of germinal vesicle (GV) and MII oocytes and significant increase of metaphase chromosome misalignment and premature chromatid segregation after meiotic maturation of oocytes, similar to human, presumably contribute to the decline in aged KM mice.

Levels and dynamic changes of serum fibroblast growth factor 23 in hypophosphatemic rickets/osteomalacia.

BACKGROUND: Hypophosphatemic rickets/osteomalacia is a group of diseases characterised by defective mineralization of bone due to hypophosphatemia and low 1,25-dihydroxy vitamin D. To explore the role of fibroblast growth factor 23 (FGF-23) in the regulation of phosphate homeostasis, we measured the circulating concentrations of this growth factor in healthy individuals and in patients with hypophosphatemic rickets/osteomalacia. METHODS: Nineteen patients with hypophosphatemic rickets/osteomalacia were included in hypophosphatemic group (HP, 12 female and 7 male, mean age was 30 years), and 19 healthy age-matched individuals served as the control group. Full length FGF-23 fragments were measured by two-site enzyme-linked immunosorbent assay. RESULTS: Mean FGF-23 concentrations were significantly higher in the HP group ((87.4 +/- 43.6) pg/ml) compared with the control group ((19.2 +/- 6.16) pg/ml; P < 0.001). In 1 patient with tumour-induced osteomalacia, serum FGF-23 concentrations were 84.1 pg/ml; these concentrations were normalized 2 hours after a hemangiopericytoma resection (7.8 pg/ml). Subsequently, serum 1,25(OH)(2) vitamin D3 concentrations significantly increased from 21.3 pg/ml to 89.3 pg/ml, and serum phosphorus levels were normalized. CONCLUSIONS: Serum FGF-23 concentrations were markedly elevated in patients with hypophosphatemic rickets. FGF-23 plays an important role in the pathogenesis of hypophosphatemic rickets/osteomalacia.

[Inhibitory effect of cucurbitacin E on the proliferation of ovarian cancer cells and its mechanism].

BACKGROUND AND OBJECTIVE: There are various biological activities of cucurbitacin E (CuE), including antitumor effect, anti-chemical carcino-genesis, liver protection, and enhancement of the immunity, and so on. This study was to investigate the effect of CuE on proliferation inhibition and apoptosis induction of ovarian cancer ES-2 cells, and to explore the mechanism. METHODS: ES-2 cells were treated with different concentrations of CuE for 24, 48, and 72 h, respectively. Cell proliferation was tested by MTT assay. The morphologic changes and apoptosis were observed under inverted microscope and fluorescent microscope. Cell cycle distribution was evaluated with flow cytometry. The expression of p-STAT3 was determined by Western blot. RESULTS: The number of ES-2 significantly decreased as the concentration of CuE increased or the time prolonged. Flow cytometry analysis showed that the ratio of ES-2 cells treated 1 micromol/L CuE for 24 h increased both in S phase [from (10.55+/-0.91)% to ( 16.31 +/- 4.61) % ] and in G(2)/M phase [from (18.53+/-1.43)% to (58.34 +/- 5.77)%], while decreased in G(1) phase [from (73.13 +/-4.70)% to (23.12 +/- 5.45)%] (P<0.05). The marked morphological changes of cell apoptosis were clearly observed in ES-2 cells treated with CuE. CuE inhibited the STAT3 phosphorylation in ES-2 cell in a dose- dependent manner. CONCLUSION: CuE can inhibit ES-2 proliferation and induce apoptosis and cell cycle arrest, which may be related to the decreased expression of the intracellular STAT3 phosphorylation.

Escin, a natural mixture of triterpene saponins, exhibits antitumor activity against hepatocellular carcinoma.

Escin, a mixture of triterpene saponins extracted from Aesculus wilsonii Rehd., was used to analyze the antitumor effect in hepatocellular carcinoma in vivo and in vitro. At a dose of 2.8 mg/kg, escin had a rather high inhibition ratio (43.5 %) on mice H22 tumor growth in vivo. The results of the SRB cell viability assay showed that escin could induce significant concentration- and time-dependent inhibition of HepG (2) cell viability. Disruption of the G (1)/S phase of cell cycle progression accompanied by the induction of apoptosis were also observed in HepG (2) cells following escin treatment. The results of pulse-field gel electrophoresis and Western blot analysis show the induction of caspase-independent apoptosis by escin. This study provides evidence that escin induces cell cycle checkpoint arrest and caspase-independent cell death in HepG (2) cells, in support of its efficacious potential as a chemopreventive agent.

Effect of fibroblast growth factor 9 on Runx2 gene promoter activity in MC3T3-E1 and C2C12 cells.

BACKGROUND: Fibroblast growth factor 9 (FGF9), expressed in brain, kidney and developing skeletal tissues, can physiologically inhibit endochondral ossification; but little is known about how FGF9 affects osteoblasts and its detailed regulatory mechanism. Here we examined the effect of FGF9 on the activity of the murine Runt-related transcription factor 2 (Runx2) gene promoter in preosteoblast MC3T3-E1 and premyoblast C2C12 cells. METHODS: Plasmids containing the Runx2 promoter region were transfected into MC3T3-E1 and C2C12 cells and stably transfected cell lines were established. The method of luciferase reporter gene activation was used to examine the effects of FGF9 on the promoter activity. RESULTS: FGF9 (10 ng/ml) increased Runx2 promoter activity in MC3T3-E1 cells. When MC3T3-E1 cells were treated with FGF9 plus the various inhibitors or activator of the intracellular signaling transducation pathways, including 10 micromol/L U0126 (the inhibitor of mitogen-activated protein kinase kinase), 10 micromol/L SB203580 (the inhibitor of p38/mitogen activated protein kinase), or 1 micromol/L C6 ceramide (an activator of mitogen activated protein kinase), the luciferase expression did not change significantly compared with that of the cells treated with FGF9 only. However, when C2C12 cells were treated with 10 ng/ml FGF9, Runx2 gene promoter activity first decreased and then increased over a period of 1 to 5 days. Among the above inhibitors, only U0126 (10 micromol/L) completely blocked the effects of FGF9 on Runx2 gene promoter activity. CONCLUSIONS: Our data showed that FGF9 can affect Runx2 gene promoter activity in MC3T3-E1 and C2C12 cells. The action of FGF9 appears to depend partly on the mitogen-activated protein kinase kinase/mitogen-activated protein kinase pathways in C2C12 cells.

[RET gene cys 634 trp mutation in a multiple endocrine neoplasia type 2A kindred].

OBJECTIVE: To identify the genotype of RET gene in one multiple endocrine neoplasia type 2A (MEN2A) kindred. METHODS: Genome DNA was extracted from peripheral blood leucocytes. The DNA sequence of gel-purified polymerase chain reaction (PCR) products was determined with the previously reported 6 pairs of primers of PCR amplification of 10, 11, 13, 14, 15, and 16 exons of RETgene. RESULTS: No abnormalities were found in exon 10, 13, 14, 15, and 16. C to G replacement in nucleotide 14 996 of exon 11 was identified in DNA samples obtained from both peripheral blood of 2 affected brothers. This missense point mutation arisen in heterozygosity and caused a substitution of Cys to Trp residue at codon 634 ( Cys 634 Trp) in RET protein. CONCLUSION: The genotype of the family is identified as Cys 634 Trp substitution of RET gene.

[Effects of different human parathyroid hormone 1-34 administration on SaoS-2 cells].

OBJECTIVE: To observe the effects of different human parathyroid hormone 1-34 (hPTH1-34) administration on SaoS-2 cells, and explore the mechanism of bone formation improvement. METHODS: Each cycle covered 48 h. SaoS-2 cells were continuously or intermittently stimulated by 50 ng/ml hPTH1-34 for 1, 3, 6, 12, and 24 h in each cycle. Total RNA was extracted by Trizol kit. Alkaline phosphatase (ALP), osteocalcin or bone Gla-containing protein (BGP) and cyclic adenosine monophosphate (cAMP) levels were measured by chemical method, radioimmunoassay and competitive protein binding method, respectively. c-fos gene expression was semi-quantified by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: ALP level was time-dependently increased in 1, 3 and 6 h stimulation, especially in 3 and 6 h (compared with control, P < 0.01; P < 0.05 or P < 0.01 compared with continuous stimulation). The cAMP level was time-dependently increased in 3 and 6 h incubation (P < 0.05 compared with control and continuous stimulation). Intermittent hPTH1-34 stimulation had more effects on cAMP level than continous action (P < 0.001). hPTH1-34 intermittent stimulation of 1, 3, and 6 h enhanced c-fos gene expression time-dependently. CONCLUSIONS: Intermittent hPTH1-34 stimulation has a stronger effect on osteoblast than continuous action, especially in 3, 6 h in each cycle intermittent stimulation. The synchronous responses of c-fos, ALP and cAMP to hPTH1-34 suggest that hPTH1-34 affect Saos-2 cells through cAMP dependent protein kinase A (PKA) pathway and c-fos gene paly an important role.

[Prospective study of pamidronate disodium in treatment of Paget's disease of bone].

OBJECTIVE: To determine the efficacy of pamidronate disodium (pamidronate) in treatment of Paget's disease of bone. METHODS: Intravenous drip of pamidronate was given at the dose of 30 - 60 mg per day for 2 - 3 weeks with a total dosage of 90 - 270 (168 +/- 84) mg to 5 patients with Paget's disease of bone, 2 males and 3 females, aged 27 - 74 (61 on average) with the course of disease of 4 - 48 years (24 years on average), all of them having multiple bone lesions, 2 being in grade 4 of pain assessment and bedridden and 3 being in grade 3 with impaired mobility. Pain assessment, biochemical markers of bone turnover, including serum alkaline phosphatase (ALP), carboxy-terminal propeptide of type I collagen (PICP), carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) and urinary hydroxyproline (HOP), and side effects of pamidronate were observed before treatment, by the end of treatment, and 4, 12, 24, and 48 weeks after treatment. RESULTS: The Pagetic bone pain was significantly reduced by the end of treatment in all patients. The degree of pain assessment declined from grade 4 to grade 2 in 2 patients, and from grade 3 to grade 1 in 3 patients. The mobility was markedly improved without bone pain 12 weeks after treatment and relief of pain lasted for 1 year in all patients. Serum ALP, PICP, ICTP and urinary HOP concentrations were significant decrease by the end of treatment. Moreover, the mean percentage decreases for above biochemical markers at 12 and 24 weeks after treatment were 50% or over. The values of serum ALP, PICP, ICTP and urinary HOP decreased from 398 u/L (median), 818 ng/L (median), (29 +/- 14) ng/L and (71 +/- 16) mg/24 h urine respectively to 159 u/L, 129 ng/L, (12 +/- 4) ng/L and (34 +/- 7) mg/24 h urine respectively 48 weeks after treatment (all P < 0.05). Side effects, including a transient increase in body temperature, skin eruption and pruritus, and a transient increase of serum aspartate aminotransferase concentration, were negligible. CONCLUSION: Intravenous infusion of pamidronate is effective on Paget's disease of bone. Pamidronate of the dose of 90 - 270 mg administered within 2 - 3 weeks produces a year-long remission. Side effects of pamidronate are slight and transient.

Expression of core binding factor alpha1 up-regulated by IGF-I, GM-CSF, and EGF through MAPK pathway in MC3T3-E1 and C2C12 cells.

AIM: To study the regulating function and mechanism of insulin-like growth factor-I (IGF-I), granulocyte-macrophage colony-stimulating factor (GM-CSF), and epidermal growth factor (EGF) on murine core binding factor alpha1 (Cbfalpha1) gene expression. METHODS: Luciferase reporter gene method and RT-PCR technique were used to examine the effects of these growth factors on the promoter activity and mRNA expression of Cbfalpha1 gene in MC3T3-E1 and C2C12 cells. RESULTS: IGF-I (from 1 nmol/L to 1 micromol/L), GM-CSF (100 nmol/L), and EGF (1 micromol/L) increased the luciferase expression in MC3T3-E1 cells (P<0.05). And mitogen-activated protein kinase (MAPK) inhibitor, PD 98059 (10 micromol/L), completely blocked IGF-1, GM-CSF, and EGF-induced expression of Cbfa1 promoter activity (P<0.01). In C2C12 cells, IGF-I (from 1 nmol/L to 10 micromol/L), GM-CSF (100 nmol/L and 1 micromol/L), and EGF (100 nmol/L) enhanced the expression of luciferase reporter plasmid driven by mCbfalpha1 promoter (P<0.05). Addition of PD 98059 also blocked the stimulatory effects of these growth factors on Cbfalpha1 promoter activity (P<0.01). Moreover, Cbfalpha1 mRNA expression was significantly increased after treatment with IGF-I (1 nmol/L, 100 nmol/L), GM-CSF (100 nmol/L, 1 micromol/L), and EGF (1 micromol/L, 100 nmol/L) in MC3T3-E1 and C2C12 cells, respectively (P<0.05). These stimulatory effects of IGF-I, GM-CSF, and EGF on Cbfalpha1 mRNA expression were abolished by PD 98059. CONCLUSION: IGF-I, GM-CSF, and EGF could increase the promoter activity and the mRNA expression of murine Cbfalpha1 gene in MC3T3-E1 and C2C12 cells. These stimulatory effects might be mediated by activating the intracellular MAPK-dependent signaling pathway.

[Evaluation of bone architecture and biomechanic properties by peripheral quantitative computed tomography in rats].

OBJECTIVES: To evaluate the value of peripheral quantitative computed tomography (pQCT) in measuring bone architecture and biomechanic properties. METHODS: 50 virgin female Wistar rats six months old were randomly divided into 4 groups: (1) 8 rats were killed as baseline group; (2) 8 rats underwent sham operation and then were killed 14 weeks after (sham operation group); (3) 16 rats underwent bilateral ovariectomy (OVX) without further intervention. Six and 14 weeks after the operation each 8 rats were killed (OVX group); and (4) 18 rats underwent OVX too. After the OVX 9 of the 18 rats were treated with 17beta-estradiol 20 micro g/kg/d IH and 9 rats were treated with estradiol valerate 800 micro g/kg/d po for 8 weeks respectively. Then the 18 rats were killed (OVX plus estrogen group, O + E group). The right tibiae of the rats were taken for histomorphometric analysis, and the right femora were prepared for pQCT scanning and bone biomechanical measurement with indentation test and three-point bending test. RESULTS: Histomorphometric analysis showed that the trabecular volume of proximal tibia (Cn-BV/TV) in the OVX group was 8.1 +/- 1.4%, significantly lower than that in the sham operation group (19.5 +/- 1.5%, P < 0.01). pQCT scanning showed that the femoral trabecular bone mineral content (Trab BMC) in the OVX group was 1.7 +/- 0.3 mg/mm, significantly lower than that in the sham operation group (3.2 +/- 0.5 mg/mm, P < 0.01) and the femoral trabecular bone mineral density (Trab BMD) in the OVX group was 158 +/- 32 mg/mm(3), significantly lower than that in the sham operation group (320 +/- 39 mg/mm(3), P < 0.01). The cancellous maximal load (Can load) of the distal shaft of femur in the OVX group was 12.5 +/- 2.5 N, significantly lower than that in the sham operation group (45.9 +/- 3.2 N, P < 0.01). The cancellous stiffness (Can Stiff) of the distal shaft of femur in the OVX group was 226 +/- 48 N/mm, significantly lower than that in the sham operation group (396 +/- 72 N/mm, P < 0.01). The Can load of O + E group was 21.8 +/- 3.7 N, significantly higher than that in the OVX group (P < 0.05). The Can Stiff of the O + E group was 382 +/- 54 N/mm, significantly higher than that in the OVX group (P < 0.05). There were no significant differences in cortical bone determined by pQCT as well as biomechanic properties in measured by three point test after OVX and estrogen treatment. A significant positive correlation was shown between Trab BMD and Cn-TV/BV and between Trab BMD and Tb N (r = 0.88 and 0.73, both P < 0.01). Similarly, both Trab BMC and Trab BMD of the femur were significantly correlated with the Can load and Can Stiff determined by indentation test (r = 0.47 - 0.68, all P < 0.01). There was also a significant correlation of parameters measured by pQCT in cortical bone with the maximal load and stiffness for the femur midshaft, and the best correlation was found between the maximal load of femur midshaft and Crt BMC and Crt A (both r = 0.76 and P < 0.01). CONCLUSION: The geometric, densitometric and mechanical properties in cortical and trabecular bones of rat can be well described by pQCT.

[Changes of urinary deoxypyridinoline crosslink/creatinine in rats after ovariectomy and anti-osteoporotic intervention].

OBJECTIVE: To observe the changes of urinary deoxypyridinoline crosslink/creatinine (UDpd/Cr) in rats after OVX and intervention by estrogen and bisphosphonate and investigate the possible application of deoxypyridinoline in osteoporosis diagnosis and treatment. METHODS: 40 female 6-month-old virginal Wistar rats were divided into 5 groups, ovariectomized or sham ovariectomized. (1) Ovxb (n = 8): sacrificed at 6 weeks after OVX; (2) Sham (n = 8): sham ovariectomized; (3) Ovxe (n = 8): sacrificed at 14 weeks after OVX; (4) O + E (n = 9):OVX + 17 beta estradiol [20 micrograms/(kg.d) ih]; (5) O + C (n = 7):OVX + cimadronate [0.2 mg/(kg.d)]; Treatment started 6 weeks after OVX and lasted 8 weeks. Rats in group 2-5 were sacrificed at 14 weeks after OVX. Urinary and serum biochemical parameters were measured, pQCT scanning of femur, bone biomechanical test in femur were determined. RESULTS: OVX resulted in increasing of UDpd/Cr 133.3% (P < 0.01). The ratio of UCa/Cr also increased in OVX groups but without any significant compared with Sham (P > 0.05). UDpd/Cr were reduced by 54.6% and 51.8% (P < 0.01) in O + E, O + C group respectively compared with Ovxe. The significant negative correlationships were found between UDpd/Cr and bone mass, BMD and biomechanic characteristics. CONCLUSIONS: UDpd/Cr ratio is a sensitive bone resorption marker, a marked changes were observed when the rats ovariectomized or treated with estradiol and cimadronate. There were best correlation between UDpd/Cr and bone mineral density and bone biomechanic characteristics. It is fair to apply UDpd/Cr ratio for osteoporosis diagnosis and treatment.

[The effects of continuous stimulation with different doses of parathyroid hormone 1-34 fragment on human SaoS-2 cells].

OBJECTIVE: To observe the effects of different doses of human parathyroid hormone fragment (hPTH)1-34 on SaoS cells and to explore the signal pathway and mechanism. METHODS: 5 x 10(4) cells/ml SaoS cells were seeded. Doses of 5, 50, 500 and 5 000 micro g/L hPTH1-34 were supplemented respectively. Total RNA was extracted by Trizol kit. Alkaline phosphatase (ALP), osteocalcin (BGP) and cAMP concentrations were measured by chemical, radioimmunoassay and competitive protein binding methods. c-fos gene expression level was semi-quantified by reverse transcriptase (RT)-PCR. RESULTS: ALP activity was higher in 500 micro g/L dose (P < 0.05 vs. control). BGP level was inhibited in 5 000 micro g/L dose (P < 0.05 vs. control and pretreatment). 50 and 500 micro g/L hPTH1-34 enhanced cAMP level significantly (P < 0.05 vs. control). No obvious increase of cAMP level was found in 5 000 micro g/L and 5 micro g/L dose groups (P > 0.05 vs. control and pretreatment). c-fos expression was higher in 50 and 500 micro g/L group. CONCLUSION: Different doses of hPTH1-34 exert distinct effects on osteoblasts. hPTH1-34 affects ALP and c-fos depending on protein kinase A signal pathway. hPTH1-34 exerts its action via regulation of osteoblasts by c-fos.