Effects of exercise combined with alendronate sodium tablets on RANKL/OPG balance and MAPK signaling pathways in ovariectomized rats

Abstract

Objective To observe the effect of exercise combined with alendronate sodium tablets(Aln)on receptor activator of nuclear factor kappa B ligand(RANKL)/osteoprotegerin(OPG)expression and mitogen-activated protein kinase (MAPK)signaling pathways in ovariectomized(OVX)rats.Methods A total of 90 6-month-old female SD rats were evenly randomized into sham group,OVX group,Aln treatment(OVX+Aln)group,exercise therapy(OVX+EX)group,and Aln combined with exercise treatment(OVX+Aln+EX)group.Eight weeks after ovariectomy,rats in the latter three groups were treated with intragastric 1mg/(kg·d)Aln and/or exercise.After 12weeks of treatment,dual-energy X-ray absorptiometry was used to examine the bone mineral density (BMD)of the left and right femurs.Enzyme-linked immunosorbent assay (ELISA)was used to determine the serum levels of RANKL and OPG.Real-time PCR was used to examine RANKLand OPG mRNA expression in bone tissues.Western blotting analysis was used to examine the phosphorylation of c-Jun N-terminal kinase(JNK),p38 MAPK (p38),extracellular-regulated kinase(ERK),and c-Fos protein expression in bone tissues.Results The following results were observed after 12-week treatment.(1)Compared with sham group,the BMD values of the left and right femurs were significantly decreased in OVX group (P0.05).The serum RANKL level was significantly increased,serum OPG level was significantly decreased,and the RANKL/OPG ratio was significantly increased (all P0.05).The RANKL mRNA expression was significantly increased and OPG mRNA expression was significantly decreased in bone tissues(all P0.05).(2)Compared with OVX group,the BMD values of left and right femurs of OVX+ Aln,OVX+EX and OVX+Aln+EX groups were significantly increased (all P0.05).The serum RANKL level was significantly decreased,serum OPG level was significantly increased,and the RANKL/OPG ratio decreased(all P0.05).The RANKL mRNA expression was significantly decreased,and OPG mRNA expression was significantly increased in bone tissues (all P0.05).(3)The femoral BMD values,serum RANKLand OPG levels,and RANKL and OPG mRNA expression in bone tissues in OVX+Aln+EX group were significantly different from those in OVX+Aln group and OVX+EX group(all P 0.05).(4)Compared with sham group,bone tissue p-JNK and c-Fos expression in OVX group was significantly increased (all P0.05).However,compared with OVX group,bone tissue p-JNK and c-Fos expression in OVX+Aln,OVX+EX and OVX+Aln+EX groups was significantly decreased(all P0.05),and there were no significant differences among the latter three groups.p-p38and p-ERK expression was similar in all groups.Conclusion Exercise combined with Aln can improve the BMD values of left and right femurs in OVX rats,which may be related to the regulation of RANKL/OPG balance and inhibition of JNK phosphorylation and c-Fos expression.