Administration of erythropoietin exerts protective effects against glucocorticoid-induced osteonecrosis of the femoral head in rats

Chen,Sen; Li,Jianping; Peng,Hao; Zhou,Jianlin; Fang,Hongsong

doi:10.3892/ijmm.2014.1644

Administration of erythropoietin exerts protective effects against glucocorticoid-induced osteonecrosis of the femoral head in rats

Authors:
- Sen Chen
- Jianping Li
- Hao Peng
- Jianlin Zhou
- Hongsong Fang
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Affiliations: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: February 5, 2014 https://doi.org/10.3892/ijmm.2014.1644
Pages: 840-848
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Accumulating evidence has indicated that erythropoietin (EPO) plays a role in anti-apoptosis and tissue protection in a number of human diseases. The present study was implemented to evaluate these anti-apoptotic and tissue-protective effects in glucocorticoid-induced osteonecrosis in rats. Osteonecrosis was induced by low-dose lipopolysaccharide and subsequent high-dose methylprednisolone pulse. Rats in the preventive group were treated with 500 U/kg/day recombinant human EPO (rhuEPO) for 1 week. Hematological and histomorphometric methods were then used to determine the effects of the administration of rhuEPO. An analysis of trabecular bone architecture was performed to evaluate bone mass change in the osteonecrosis zone. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was performed to determine the apoptotic index of osteoblasts and osteocytes. Immunoblot analysis was performed to assess the expression of caspase-3 and vascular endothelial growth factor (VEGF) in the femoral head. Treatment with rhuEPO greatly improved the histological performance. Additionally, the incidence of osteonecrosis markedly decreased in the rats in the rhuEPO-treated group (22.2%) compared with the control group (66.7%). Furthermore, the expression of caspase-3 markedly decreased in the rhuEPO-treated group. Consistently, the apoptosis of osteoblasts and osteocytes, as determined by TUNEL assays, was inhibited following the administration of rhuEPO. By contrast, the expression of VEGF increased in the osteonecrosis zone in the rats treated with rhuEPO. The results from the present study demonstrate that EPO exerts prominent protective effects against glucocorticoid-induced osteonecrosis of the femoral head in rats by inhibiting the apoptosis of osteoblasts and osteocytes and increasing the expression of VEGF.

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