Calycosin attenuates osteoporosis and regulates the expression of OPG/RANKL in ovariectomized rats via MAPK signaling.

We aimed at exploring the effect of calycosin (CA) on osteoporosis in ovariectomized (OVX) rats. Sprague-Dawley (SD) rats were divided into five groups: Sham group, OVX group, OVX group treated with estradiol valerate (EV), CAL group treated with 15 mg/kg/d of CA and CAH group treated with 30 mg/kg/d of CA for 12 weeks. Bone mineral density (BMD), histopathology, body weight, parameters in serum and urine were observed. Gene expression and protein level of OPG/RANKL were also studied by real-time PCR and western blot, respectively. We further identified the effect of CA on mitogen-activated protein kinase (MAPK) signaling. In comparison with OVX rats, CAL and CAH significantly increased the BMD by 8.3% and 19.0%. Treatment with CA notably inhibited the excretion of Ca, P and Cr. CAH also significantly increased the level of alkaline phosphatase (ALP) and decreased the level of tartrate-resistant acid phosphatase (TRAP) in serum of OVX rats. CA could improve the trabecular bone area, and increased the trabecular number and the trabecular connection after 12-week. CA also increased the expression of osteoprotegerin (OPG) and decreased the Receptor Activator for Nuclear Factor-κB Ligand (RANKL) mRNA expression compared with the OVX rats. In addition, CA could effectively decrease the phosphorylation of MAPKs induced by ovariectomy. In conclusion, CA had remarkable antiosteoporotic activity and therefore can be a promising candidate for the treatment of postmenopausal osteoporosis.