Comparison on the Efficacy of Bortezomib and Pamilophosphate in the Rat Model of Disuse Osteoporosis
OBJECTIVE:To compare the efficacy of bortezomib and pamilophosphate in the rat model of disuse osteoporosis(DOP).METHODS:Forty 16-week-old male SD rats were randomly divided into the control group,sham surgery group,model group,pamilphosphate treatment group and bortezomib treatment group,with 8 rats in each group.DOP rat model was established.The microstructural parameters of hind limb tibia were determined by micro-CT.Serological indexes receptor activator of nuclear factor-κB ligand(RANKL)/osteoprotegerin(OPG)concentration ratio,serum Sclerostin and alkaline phosphatase(ALP)levels were determined by enzyme linked immunosorbent assay.The mRNA expression levels of bone resorption-related factors type I procollagen amino-terminal prepeptide(PINP),C-terminal crosslinking telopeptide of type I collagen(CTX)-1,matrix metalloproteinase(MMP)-3 were determined by quantitative polymerase chain reaction.Signaling axis of Calcineurin/nuclear factor of activated T-cells isoform(NFAT)and signaling pathway of glycogen synthase kinase-3β(GSK3β)/protein kinase B(Akt),a key transcription factor for osteogenic differentiation,were determined by Western blotting.RESULTS:Compared with sham surgery group,bone volume fraction(BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th),connectivity density(Conn.D),structural model index(SMI),bone mineral density(BMD)and trabecular separation(Tb.Sp)of the posterior limb tibia in model group rats decreased,trabecular separation(Tb.Sp)increased;serum RANKL/OPG concentration ratio and serum sclerostin level increased,serum ALP level decreased;the relative expression levels of PINP and CTX-1 mRNA in bone tissues decreased,while the relative expression levels of MMP-3 and MMP-9 mRNA increased,the relative expression levels of Calcineurin decreased;the relative expression levels of p-Akt decreased,and the relative expression levels of p-GSK3 increased,with statistically significant differences(P<0.05).Compared with the model group,the pamilphosphate treatment group and bortezomib treatment group partially reversed the above indicators(including BV/TV,Tb.N,Tb.Th,Tb.Sp,Conn.D,SMI and BMD in posterior limb tibia,serum RANKL/OPG concentration ratio,levels of Sclerostin and ALP,the relative expression levels of MMP-3 and MMP-9 mRNA in bone tissues,the relative expression levels of Calcineurin in bone tissues,and the relative expression levels of p-Akt and p-GSK3β in bone tissues),with statistically significant differences(P<0.05).The relative expression levels of PINP and CTX-1 mRNA and the relative expression levels of NFAT in bone tissues of rats in bortezomib treatment group increased,with statistically significant difference(P<0.05).Compared with the pamilophosphate treatment group,bortezomib treatment group had a more significant effect on reversing the above indicators,the differences were statistically significant(P<0.05).CONCLUSIONS:The efficacy of bortezomib for DOP rat model is better than that of pamilophosphate.
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