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Synergistic effects of erythropoietin and selenium enhance bone regeneration in ovariectomized rats
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DOI：10.1007/s10856-026-07088-1.png)
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Abstract
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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.
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