title: Administration of erythropoietin exerts protective effects against glucocorticoid-induced osteonecrosis of the femoral head in rats.
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.
authors: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Sen
authors: S
authors: Chen
authors: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Jianping
authors: J
authors: Li
authors: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Hao
authors: H
authors: Peng
authors: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Jianlin
authors: J
authors: Zhou
authors: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors: Hongsong
authors: H
authors: Fang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004906:Erythrocyte Count; D004921:Erythropoietin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D005270:Femur Head / Q000187:drug effects / Q000473:pathology; D005271:Femur Head Necrosis / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D005938:Glucocorticoids / Q000009:adverse effects*; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D008297:Male; D009929:Organ Size / Q000187:drug effects; D020011:Protective Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D006454:Hemoglobins; D020011:Protective Agents; D014280:Triglycerides; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D002784:Cholesterol; D053148:Caspase 3