Donghai Li1, Qinsheng Hu1, Gang Tan2, Xiaowei Xie3, Zhouyuan Yang1, Pengde Kang4. 1. Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, People's Republic of China. 2. Department of Orthopedics, Orthopedic Hospital of Mianyang, Mianyang, People's Republic of China. 3. Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China. 4. Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, People's Republic of China. Electronic address: kangpengde69@126.com.
Abstract
BACKGROUND: This study aimed to determine whether erythropoietin could repair glucocorticoid-induced osteonecrosis of the femoral head after the systemic or local administration of recombinant human erythropoietin. MATERIALS AND METHODS: Gelatin microspheres were used to load recombinant human erythropoietin for local delivery. Forty-eight Wistar rats were included in the glucocorticoid-induced osteonecrosis of the femoral head model and randomly divided into the placebo, systemic erythropoietin and local erythropoietin groups. Eight weeks later, all rats were killed and their tissues were subjected to radiographic, histological, histometric, quantitative polymerase chain reaction and western blot analyses. RESULTS: Our results show that the use of recombinant human erythropoietin increased bone volume, trabecular number, trabecular thickness and trabecular separation compared with the placebo. Erythropoietin administration significantly improved the expression of runt-related transcription factor 2, alkaline phosphates, hypoxia-inducible factor-1α and vascular endothelial growth factor in the femoral head. We also found that the local injection of erythropoietin could better mediate hypoxia-inducible factor-1α-controlled osteogenic and angiogenic factor expression and better repair the glucocorticoid-induced osteonecrosis of the femoral head. CONCLUSIONS: The use of recombinant human erythropoietin exerted effects on improving the bone structures in glucocorticoid-induced osteonecrosis of the femoral head and up-regulated the expression of runt-related transcription factor 2, alkaline phosphates, hypoxia-inducible factor-1α and vascular endothelial growth factor. It provided a novel idea that erythropoietin administration could repair glucocorticoid-induced osteonecrosis of the femoral head by improving bone formation and angiogenesis and may be associated with the hypoxia-inducible factor-1α pathway. The sequential delivery of erythropoietin from gelatin microspheres seems worth recommending.
BACKGROUND: This study aimed to determine whether erythropoietin could repair glucocorticoid-induced osteonecrosis of the femoral head after the systemic or local administration of recombinant humanerythropoietin. MATERIALS AND METHODS: Gelatin microspheres were used to load recombinant humanerythropoietin for local delivery. Forty-eight Wistar rats were included in the glucocorticoid-induced osteonecrosis of the femoral head model and randomly divided into the placebo, systemic erythropoietin and local erythropoietin groups. Eight weeks later, all rats were killed and their tissues were subjected to radiographic, histological, histometric, quantitative polymerase chain reaction and western blot analyses. RESULTS: Our results show that the use of recombinant humanerythropoietin increased bone volume, trabecular number, trabecular thickness and trabecular separation compared with the placebo. Erythropoietin administration significantly improved the expression of runt-related transcription factor 2, alkaline phosphates, hypoxia-inducible factor-1α and vascular endothelial growth factor in the femoral head. We also found that the local injection of erythropoietin could better mediate hypoxia-inducible factor-1α-controlled osteogenic and angiogenic factor expression and better repair the glucocorticoid-induced osteonecrosis of the femoral head. CONCLUSIONS: The use of recombinant humanerythropoietin exerted effects on improving the bone structures in glucocorticoid-induced osteonecrosis of the femoral head and up-regulated the expression of runt-related transcription factor 2, alkaline phosphates, hypoxia-inducible factor-1α and vascular endothelial growth factor. It provided a novel idea that erythropoietin administration could repair glucocorticoid-induced osteonecrosis of the femoral head by improving bone formation and angiogenesis and may be associated with the hypoxia-inducible factor-1α pathway. The sequential delivery of erythropoietin from gelatin microspheres seems worth recommending.