A Combination of Granulocyte Colony-Stimulating Factor and Stem Cell Factor Ameliorates Steroid- Associated Osteonecrosis in Rabbits

Abstract

ObjectiveBone marrow-derived stem cells (BMSC) have been highlighted for the treatment of osteonecrosis (ON) before collapse of the femoral head. In our study, the potential of granulocyte colony-stimulating factor/stem cell factor (G-CSF/SCF)-mobilized BMSC to repair steroid-associated ON was assessed in rabbits.MethodsON was induced by low-dose lipopolysaccharide and subsequent pulsed high-dose methylprednisolone. Rabbits in the treated group were subjected to subcutaneous injections of GCSF at a dose of 100 μg/kg and SCF 25 μg/kg per day for 5 days; rabbits in the control group were given saline. Blood samples were collected and serum osteocalcin was detected by ELISA. Radiological analysis was performed by magnetic resonance imaging (MRI). Then bilateral femora and humeri were harvested and processed to paraffin sections and hard-tissue sections for immunohistochemical, histologic, and histomorphometric analysis.ResultsThe mean number of leukocytes and relative numbers of mononuclear cells increased significantly after mobilization. All rabbits displayed a marked increase in osteocalcin protein expression in response to G-CSF/SCF. MRI scans showed a reactive interface between the necrotic and reparative zones after G-CSF/SCF administration. Quantitative analysis showed that new vessel formation was 3.3-fold greater and vessel density was 2.6-fold greater in the treatment group than the control group. The histologic and histomorphometric analysis revealed that the new bone volume was significantly higher in the G-SCF/SCF group than in the control group at 4 weeks.ConclusionG-CSF/SCF-induced mobilization of BMSC in the necrotic foci may represent a promising strategy for promoting functional bone repair of early-stage ON.