Icariin Alleviates Glucocorticoid-Induced Osteoporosis through EphB4/Ephrin-B2 Axis

PURPOSE: Glucocorticoid (GC) is the most important risk factor for osteoporosis (OP); in the present study, we examined the potential mechanism of icariin, a natural bioactive compound isolated from the traditional Chinese herbal Epimedium, for GC-induced OP to explore its potential therapeutic effect. METHODS: We used a GC-induced OP mice model and treated with icariin. Pathological changes were measured by H&E staining, and the effects of icariin on osteoblasts and osteoclasts were measured by immunohistochemistry (IHC) staining and western blot (WB) analyses, while trabecular bone parameters were detected by micro-CT imaging in vivo. RESULTS: The results showed that in GC-induced OP symptoms, icariin treatment significantly increased the density of the trabecular bone when exposed to GC, revealed by H&E staining and micro-CT imaging. IHC staining showed that GC-induced OP had a lower EphB4 expression and higher Ephrin-B2 expression, but icariin could promote EphB4 while suppressing Ephrin-B2 expression. The WB results also provided evidence of the same protein expression trend, showing that the osteoblast marker OCN and the EphB4 downstream factor RhoA in the GC group were decreased, while both OCN and RhoA expression were significantly increased and the Ephrin-B2 downstream factor Grb4 in in GC group was increased after icariin treatment. CONCLUSION: Icariin could improve the characteristics of OP through regulating the balance of the EphB4/Ephrin-B2 pathway. Further preclinical trial is needed to provide certainty of clinical benefits for OP patients.