losartan-potassium and Osteonecrosis

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.. 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.. 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.. 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.

Topics: Animals; Erythropoietin; Femur Head; Gelatin; Glucocorticoids; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Male; Microscopy, Electron, Scanning; Microspheres; Osteonecrosis; Pilot Projects; Rats; Rats, Wistar; Recombinant Proteins; Signal Transduction

Long‑term administration of glucocorticoid hormones is considered one of predominant pathological factors inducing osteonecrosis of the femoral head (ONFH) development and progression, in which reduction of blood supply leads to a progressive bone loss and impairment of bone structure in the majority of cases. In a non‑hematopoietic system, erythropoietin (EPO) can stimulate angiogenesis and bone regeneration. However, the specific mechanism underlying the role of EPO in ONFH remains to be elucidated. Therefore, the purpose of this study was to determine the effect of EPO on the prevention of bone loss in ONFH. Male C57BL/6J mice 3 months old were divided into two groups: EPO group and control groups. ONFH was established by the administration prednisolone (PDS, 100 mg/kg) with co‑treatment of lipopolysaccharide (LPS, 1 mg/kg). ONFH mice received recombinant mouse EPO (500 U/kg/day) or saline intramuscularly. The mice were sacrificed at 2, 4, 6 and 8 weeks following the initiation of treatment. Alterations in the general architecture and histomorphology of the right femoral head were determined by hematoxylin and eosin staining and micro computed tomography (micro‑CT). The expression of runt‑related transcription factor 2 (Runx2), osteocalcin, vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule (CD31) in the femoral head was tested by immunohistochemistry. Terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling (TUNEL) assay was performed to detect apoptosis in femoral heads. Micro‑CT data revealed that EPO significantly improved bone volume/total volume and bone mineral density following 6 and 8 weeks of treatment. Histological analysis further demonstrated that EPO treatment improved the arrangement of trabeculae, thinning of trabeculae and other fractures in femoral heads, especially following 6 and 8 weeks of treatment. Immunohistochemical analysis suggested that EPO treatment up‑regulated the expressions of Runx2, osteocalcin, VEGF and CD31 at 4 and 8 weeks. The TUNEL apoptosis assay suggested that EPO intervention reduced apoptosis in avascular ONFH. Therefore, EPO prevents bone loss in ONFH in mice through enhancing Runx2‑mediated osteogenesis, VEGF‑mediated angiogenesis and inhibition of cell apoptosis.

Topics: Animals; Apoptosis; Biomarkers; Bone Resorption; Disease Models, Animal; Erythropoietin; Femur Head; Immunohistochemistry; Male; Mice; Organ Size; Osteonecrosis; X-Ray Microtomography