A mouse model of osteonecrotic femoral head induced by methylprednisolone and lipopolysaccharide

Abstract

Introduction: Osteonecrosis of the femoral head is caused by various factors, including prolonged use of steroid drugs, use of alcohol, vascular injuries and hemoglobinopathies. This study aims to develop a mouse model for glucocorticoid-induced avascular necrosis (AVN) of the femoral head.

Methods: Adult mice were randomly divided into two groups: experimental and control. Group A (the experimental group) was given (via intramuscular injection) 10 mg/kg of lipopolysaccharide (LPS) and 30 mg/kg of methylprednisolone (MPS). Each mouse additionally received MPS in divided oral doses of 13 mg/kg for 10 consecutive days. Group B (the control group) received normal saline at the same location and same volume as those in Group A. Histological changes of the femoral heads were observed by electron microscopy at 3, 5, and 7 weeks after the last chemical injection. The percentage of empty lacunae was measured randomly and the expression of fibrocartilage was evaluated using an image analyz­ing system. The expression of CD31 and VEGF-R2 were observed by immunohistochemistry. The bone marrow-derived mononuclear cells were stained with propidium iodide and cell cycle was analyzed by flow cytometry.

Results: The results showed that at weeks 3 and 5, mice in Group A showed an increase in body weight. From weeks 5 to 7, mouse body weight in both groups remained constant. No difference in bone morphology was observed at week 7. The percentage of empty lacunae was 5.87  2.49% at week 5 and 21.58  8.10% at week 7. After 7 weeks, chondrocyte degeneration and fibrocartilage expression were observed. Moreover, the density of CD31 and VEGF-R2 markers increased in the femoral head. The rate of apoptosis in the bone marrow increased at week 3 then decreased.

Conclusion: The data show that MPS, combined with LPS, can induce in mice features typical of early AVN of the femoral head.