Synergistic effects of erythropoietin and selenium enhance bone regeneration in ovariectomized rats

Osteoporotic bone defects present formidable clinical challenges due to the limited capacity for natural bone repair. Erythropoietin (EPO) and Selenium (Se) have both demonstrated significant efficacy in enhancing bone regeneration; however, it remains unclear whether the combination of EPO and Se can further augment bone repair in the context of estrogen deficiency-induced osteoporosis. We undertook a study aimed at exploring the potential effects of localized implantation of materials incorporating EPO and/or Se on bone regeneration in rats subjected to osteoporosis via bilateral ovariectomy. Our observations revealed that local administration of EPO and Se over a period of 12 weeks effectively accelerated the healing process of osteoporotic bone defects, as evidenced by Micro-CT imaging and hematoxylin-eosin (HE) pathological staining. In addition, our findings from immunofluorescence assays, immunohistochemical analyses, and PCR testing indicate that local treatment with Se/EPO led to heightened expression levels of skeletal osteocalcin (OC), nuclear factor erythroid 2-related factor 2 (NRF2), and vascular endothelial growth factor (VEGF), alongside reduced expression levels of tartrate-resistant acid phosphatase (TRAP) in osteoporotic rats. Furthermore, this topical treatment exhibited conspicuous alterations in the expression profiles of key genes including osteoprotegerin (OPG), Runt-related transcription factor 2 (RUNX2), receptor activator of nuclear factor kappa-B ligand (RANKL), and sclerostin (SOST). Our results substantiate that localized administration utilizing Se/EPO holds considerable promise as an effective strategy for expediting the healing process associated with bone defects in cases of postmenopausal osteoporosis.