Effect of PERK signaling pathway on osteoblast differentiation of female rats with experimental postmenopausal osteoporosis / 吉林大学学报(医学版)

ABSTRACT

Objective:To investigate the changes of PERK,Runx2,osterix,RANKL and OPG in bone tissue of the female rats with experimental postmenopausal osteoporosis(PMOP)before and after treatment,and to elucidate the role of PERK signaling pathway in PMOP.Methods:The ovariectomized rats were reproduced to osteoporosis models.A total of 45 rats were divided into normal control group(the rats didn't receive any treatment,n=15),osteoporosis group(the rats were ovariectomized,n=15)and osteoporosis treatment group (the ovariectomized rats were injected with estrogen through caudal vein,n=15).The changes of serum collagenⅠ(Col Ⅰ),alkaline phosphatase(ALP)and osteocalcin(OCN)of the rats in various groups were observed. Three months after feeding,the femoral shaft of the rats in various groups were taken for pathological section.The gene expression levels of PERK,ATF4,Runx2,osterix,RANKL and OPG in bone tissue of the rats in various groups were detected by RT-PCR;the protein expression levels of PERK,ATF4,Runx2,osterix,RANKL and OPG were detected by Western blotting method.Results:Compared with control group,the levels of serum Col Ⅰ,ALP and OCN in the rats in osteoporosis group were significantly decreased(P<0.05 or P<0.01);compared with osteoporosis group,the levels of serum ColⅠ,ALP and OCN of the rats in osteoporosis treatment group were significantly increased(P<0.01).Compared with control group,the gene expression levels of PERK, ATF4,Runx2 and osterix in bone tissue of the rats in osteoporosis group were significantly decreased(P<0.01), and the gene expression level of RANKL was increased(P<0.01);compared with osteoporosis group,the gene expression levels of PERK,ATF4 Runx2 and osterix in bone tissue of the rats in osteoporosis treatment group were significantly increased(P<0.01),and the gene expression level of RANKL was significantly decreased(P<0.01).Compared with control group,the protein expression levels of PERK,Runx2 and osterix in bone tissue of the rats in osteoporosis group were significantly decreased(P<0.05 or P<0.01),and the protein expression level of RANKL were increased(P<0.05 or P<0.01);compared with osteoporosis group,the protein expression levels of PERK,Runx2 and osterix in bone tissue of the rats in osteoporosis treatment group were significantly increased(P<0.05 or P<0.01),and the protein expression level of RANKL was significantly decreased(P<0.01).The HE staining results showed that compared with control group,the bone resorption pits in bone tissue of the rats in osteoporosis group became large with the increased bone absorption,which caused bone loss;compared with osteoporosis group,the resorption in bone tissue of the rats in osteoporosis treatment group was decreased,and the bone structure returned to normal.Conclusion:After the female rats are ovariectomized and injected with estrogen,the expression trends of PERK and osteoblast transcription factors Runx2 and osterix are consistent,in contrast with the osteoclast transcription factor RANKL expression,suggesting that the osteoblast function is reduced and it is related to the decreased expression of PERK in PMOP onset.