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Low dose erythropoietin stimulates bone healing in mice
Author(s) -
Garcia P.,
Speidel V.,
Scheuer C.,
Laschke M.W.,
Holstein J.H.,
Histing T.,
Pohlemann T.,
Menger M.D.
Publication year - 2011
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21219
Subject(s) - bone healing , erythropoietin , medicine , progenitor cell , callus , osteoblast , nonunion , bone marrow , immunohistochemistry , pathology , stem cell , anatomy , chemistry , biology , microbiology and biotechnology , biochemistry , genetics , in vitro
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. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:165–172, 2011