Effects Of Osteogenic Growth Peptide C-terminal Pentapeptide Darivates 74F,110L On Bone Metabolism In Ovariectomy Rats

ObjectiveTo investigate the effects of OGP(10-14) derivates 74F,110L on bone metabolism of ovariectomy-reduced osteoporosis rats.74F,110L were given by the program of 5-5-5 ADFR.To compare them with the effects of continual or discontinual use of alendronate sodium,and evaluate which is the best.MethodFifty female unmated and there months old SD rats were used in the experiment. Fouty-two of them were bilaterally ovariectomied and randomly devided into 5 groups,the others were SHAM-operated.Group 1 and 2 were given 74F or 110L in 5-5-5ADFR;group 3 was given Alen in 5-5-5DFR alone;group 4 was given Alen continuely;group 5 and 6 were given phosphate buffered solution(PBS). Concentrations of drugs were 74F,110L,PBS 10nmol/100gW/d,Alen 10ug/100gW/d. Group 1 and 2 were experimental group,the others were control group.All drugs were given from the next day of operation.After twelve weeks of treatment,all rats were killed by bloodletting at femoral artery.Changes of indexes such as weight,wet weight and pathological structure of liver,kidney and uterus,serumal calcium,phosphorus,alkaline phosphatase and bone gla protein,BMD,ratio of ashy weight to dry weight of femor,metrological and biomechanical index were observed.Result1.weight The extent of weight increase in all ovariectomied groups were higher than SHAM.No obvious difference between group Alen,Alen DFR and O. Increment of weight in experimental groups were lower than them.2.wet weight and pathological structure of internal organs Wet weight and pathological structure of liver and kidney were not obviously different among groups. Wet weight of uterus in all post-ovariectomy groups were lower than SHAM,but no obvious difference among of them.Compared to group O,uterus of ovariectomied groups were shrinked and number of gland were decreased.Pathological structure of uteruses in all ovariectomied group were similar.3.serological indexes The level of serumal calcium and phosphorus was similar.Number of ALP and BGP in ovariectomied group were higher than SHAM, meanwhile,which of experimental groups were higher than group Alen and Alen DFR,but lower than O.There were no statistical difference between experimental groups.4.bone metrological indexes Compared with SHAM,morphological indexes BV/TV,Tb.Th and Tb.N in ovariectomied group were decreased,Tb.Sp,OV/BV and OS/BS were increased;Dynamical indexes sLS/BS,dLS/BS,MS/BS were increased. BV/TV,Tb.Th and Tb.N in group Alen,Alen DFR,74F and 110L were higher than O,Tb.Sp of them were lower than O.sLS/BS,dLS/BS and MLT were decreased. MS/BS,MAR,BFR(T) were increased in experimental groups,but decreased in control groups.The extent of increased or decreased was more obvious in experimental groups.Between the two experimental groups,OV/BV,OS/BS of 74F were higher than 110L,other indexes were not obviously different.5.BMD BMD of either lumbar or femur in post-ovariectomy groups were lower than SHAM.All treatment groups had relatively high BMD,and experimental groups were more obvious.BMD in the group that Alen was used continually was better than it in discontinued used group.No obvious difference between experimental groups.6.Ratio of ashy weight to dry weight of femor The ratio of O was obviously lower than SHAM;the ratio of each treatmental group was higher than which of group O.The ratio of Alen was the highest,which was followed by Alen DFR.Which of experimental groups were lowest,and without obvious difference between them.7.biomechanical indexes(1)lumbar compression test Comparing with SHAM,all indexes in O were decreased,but the difference between them was no statistical significance.Indexes in treatment group were higher than O,which of experimental groups were the highest.The extent of increase in Alen were more than Alen DFR.No statistical significance between experimental groups.(2)three points bending test of femur Indexes of O were lower than SHAM except bending energy, but all differences were no statistical significance.Some indexes such as the largest load,elastic load,bending elastic modulus and bending rigidity modulus in treatment groups were obviously higher than O.These indexes in experimental groups were higher than group Alen and Alen DFR,but no statistical difference between the two later groups.Comparing with O,the largest flexibility and bending energy in group Alen and bending tenacity modulus in group Alen DFR were decreased,however,the above-mentioned indexes in experiment groups were increased.No statistical difference between the two experimental groups.ConclusionOvariectomy could cause obvious weight increase,OGP(10-14) derivate may cut down the extent of increase.OGP(10-14) derivate could not effect liver and kidney and also did not stimulate uterus in short-term application.OGP(10-14) derivate could obviously raise BMD of osteoporosis rats reduced by ovariectomy, improve its microstructure and biomechanics function of bone,increase its bone mineralization and elevate its mineral content of bone.