Effects of antidepressants on osteoporosis related protein OPG, RANKL and RANK in ovariectomized rat model with depressive disorder

Abstract

Objective To investigate the effects of antidepressant therapy on whole regulating function of OPG/RANKL/RANK system in ovariectomized(OVX) rat model with depressive disorder. Methods Forty sexually mature female SD rats were used as subjects. The rats were randomly divided into 8 groups as following: sham group(Sn), depression group(Dn), the OVX group(On), the OVX with depression group(ODn), OVX with depression + sertraline group (ODs), and OVX with depression + citalopram (ODx), OVX with depression + reboxetine group(ODr), OVX with depression + venlafaxine group(ODw). Bilateral oophorectomy was applied to establish the ovariectomized rats model.Chronic unpredictable mild stress(CUMS) was used to estalish depression model. Open-field test and sugar consumption experiment were applied before the experiment and the 28th day of the experiment. Immunohistochemistry and Quantitative Real-time PCR were used to observe the expression of OPG, RANKL and RANK. Results After chronic unpredictable mild stress the scores of horizontal motion, vertical motion and percentage of sugar consumption experiment in Dn group were decreased contrast to the in control Sn group (P<0.05)and the scores in ODn group were decreased in contrast to the On group (P<0.05). The protein and gene expression of RANK in Dn group and On group were increased in contrast to the Sn group (P<0.05). The protein and gene expression of RANKL in Dn group and On group were increased in contrast to the Sn group (P<0.05). The gene expression of OPG in ODs group(5.94±0.79), ODw group(5.99±1.08) and ODr group(6.59±0.69)was decreased in contrast to the ODn group(4.96±0.51)(P<0.05). The gene expression of RANK in ODs group(2.82±0.23), ODx group(3.03±0.04)was increased in contrast to the ODn group(3.44±0.18)(P<0.05). The gene expression of RANKL in ODs group(4.82±0.94), ODx group(5.00±0.82) and ODw group(5.23±0.88)was decreased in contrast to the ODn group(3.69±0.69)(P<0.05). Conclusion The expression of RANK and RANKL in femoral neck is increased both in depressive disorder model rats and ovariectomized model rats.The antidepressant can up-regulate the expression of RANK, and down-regulate the expression of OPG and RANKL in the OVX with depression group. Of the effect, sertraline is the strongest, however reboxetine mesylate is the poorest. Key words: Antidepressant; Depressive disorder rats model; Ovariectomized rats model; Osteoprotegerin; Receptor activator of NF-κB