title: Low dose erythropoietin stimulates bone healing in mice.
abstract: Beyond its classical role in regulation of erythropoiesis, erythropoietin (EPO) has been shown to exert protective and regenerative actions in a variety of non-hematopoietic tissues. However, little is known about potential actions in bone regeneration. To analyze fracture healing in mice, a femoral 0.25 mm osteotomy gap was stabilized with a pin-clip technique. Animals were treated with 500 U EPO/kg bw per day or with vehicle only. After 2 and 5 weeks, fracture healing was analyzed biomechanically, radiologically and histologically. Expression of PCNA and NFκB was examined by Western blot analysis. Vascularization was analyzed by immunohistochemical staining of PECAM-1. Circulating endothelial progenitor cells were measured by flow-cytometry. Herein, we demonstrate that EPO-treatment significantly accelerates bone healing in mice. This is indicated by a significantly greater biomechanical stiffness and a higher radiological density of the periosteal callus at 2 and 5 weeks after fracture and stabilization. Histological analysis demonstrated significantly more bone and less cartilage and fibrous tissue in the periosteal callus. Endosteal vascularization was significantly increased in EPO-treated animals when compared to controls. The number of circulating endothelial progenitor cells was significantly greater in EPO-treated animals. The herein shown acceleration of healing by EPO may represent a promising novel treatment strategy for fractures with delayed healing and non-union formation.
authors.affiliation: Department of Trauma-, Hand- and Reconstructive Surgery, University of Saarland, Homburg/Saar, Germany. patric.garcia@uks.eu
authors.forename: P
authors.initials: P
authors.lastname: Garcia
authors.forename: V
authors.initials: V
authors.lastname: Speidel
authors.forename: C
authors.initials: C
authors.lastname: Scheuer
authors.forename: M W
authors.initials: MW
authors.lastname: Laschke
authors.forename: J H
authors.initials: JH
authors.lastname: Holstein
authors.forename: T
authors.initials: T
authors.lastname: Histing
authors.forename: T
authors.initials: T
authors.lastname: Pohlemann
authors.forename: M D
authors.initials: MD
authors.lastname: Menger
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015153:Blotting, Western; D001861:Bone Regeneration / Q000187:drug effects*; D002146:Bony Callus / Q000473:pathology; D004921:Erythropoietin / Q000008:administration & dosage*; D005434:Flow Cytometry; D006454:Hemoglobins / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D031222:Patellar Dislocation / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D011859:Radiography
chemical_list: D006454:Hemoglobins; D004921:Erythropoietin