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The Effects Of C-terminal Pentapeptide Of Osteogenic Growth Peptide [OGP10-14] And Its Analogue G48A On Bone Metabolism In Rats

Posted on:2004-12-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:X Y DingFull Text:PDF
GTID:1104360092498365Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
objective: To investigate the effects of OGP(10-14) and its analogue G48A on biochemical markers of bone turnover, bone mineral density(BMD), histomorphometry and biomechanical properties in ovariectomized rats while the relationships between BMD, biomechanics and histomorphometric parameters were explored. Methods: Eighty-six female SD rats, four months old, were divided into following groups by body weight randomly: OP-prevention group and OP-therapy group. The ovariectomized rats were used as a model for osteoporosis. The prevention group was further subdivided into seven groups(n= 8/group): shamed-operated group(SHAM), Ovariectomized group(OVX), Alendronate-therapy group(ALEN), G36G high dosage-therapy group (G36GH), G36G low dosage-therapy group (G36GL), G48A high dosage -therapy group (G48AH), G48A low dosage -therapy group (G48AL). The rats of prevention groups were injected subcutaneously with phosphate buffered saline (PBS) on SHAM and OVX group or G36G, G48A , alendronate on other groups once per day for 9 weeks one day after the ovariectomyseparately, then sacrificed. The therapy group was further subdivided into six groups(n= 5/group) :shamed-operated group(SHAM-T), Ovariectomized group(OVX-T), Risedronate-therapy group(RISE-T), Risedronate with G36G therapeutic alliance group(36GRI-T), G36G high dosage-therapy group (G36G-T), G48A high dosage-therapy group (G48A-T). The rats of therapy groups were injected subcutaneously with PBS on SHAM and OVX group or G36G, G48A, Risedronate on other groups once per day for periods of 9 weeks initiated 15 weeks after ovariectomy separately, then sacrificed. Lumbar spine,the bilateral tibia and femur were dissected out. Serum BGP and IGF-2 levels were determined by radioimmunoassay , while The morphological and dynamic parameters for bone histomorphometry , biochemical markers for bone formation and other indices of bone metabolism were measured. Biomechanical property parameters of femora and lumbar spine (L5) were measured with the three point bending tests and compressive test. The BMD of total femur .distal femur metaphysis and L1-4 were measured by dual energy X-ray absorptiomtry (DEXA) using DMS equipment while histomorphometry of proximal tibia undecalcif ied specimen sections were performed which include trabecular volume, trabecular thickness, dynamic data , et al. The relationship between BMD, biomechanic characters and histormorphometry in OP-prevention group were investigated. These data were analyzed by SPSS 10. 0 software with analysis of variance and correlation. Results: Akaline phosphatase activity levels were not statistically significantly different in the prevention and therapy groups. An elevation of BGP serum level were observed in OVX and ALENgroup as compared with G48AH group however the descent of IGF-2 serum level were determined in G36GH, G48AH group as compared with SHAM group. The results showed that both G36G and G48A had significant stimulation on bone formation as the tetracycline labeling on the trabecular bone surface and the rate of bone formation while no significant effect on the biomechanics, but both of them could not completely prevent bone loss in OVX rats. The ratio of femora ash weight to dry weight(AW/DW) and BMD of total femur, distal metaphysis , L1-4 in OVX and OVX-T group were significantly lower than in SHAM group, while the above-mentioned indices were remarkably increased in ALEN group than others. There was only an increased trend of BMD on the three sites of bone in G36GH, G36GL, G48AH, G48AL group as compared with OVX group. Bone histomorphometry in the OVX group was showed significant decrease on trabecular bone volume%total tissue (TBV/TTV), mean trabecular plate thickness(MTPT), mean trabecular plate density( MTPD) while mean trabecular plate spacing( MTPS) seemed to be higher than other groups. In the G36GH and G48AH groups, parameters of the TBV/TTV, trabecular bone volume%total sponge( TBV/SBV), MTPT were statistically increased and parameters of MTPS, trabecular surface%volume...
Keywords/Search Tags:Osteogenic growth peptide, Analogue, Osteoporosis, Ovariectomized, Bone turnover, Biochemical markers, Bone mineral density, Histomorphometry, Biomechanics
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