Changes of gene expression profiling and pathways related fat metabolisim in femoral head of steroid-induced osteonecrotic rats

Abstract

Objective To understand the changes of gene expression profiling and pathways related to fat metabolism in femoral head of steroid-induced osteonecrotic rats in contribution to pathogenesis of steroid-induced osteonecrosis. Methods We applied lipopolysaccharide (LPS) and methylprednisolone (MPSL) to prepare a rat model of steroid-induced osteonecrosis (SIO). Rats were divided into two groups: normal (N) group and model (M) group. All rats were sacrificed after 6 weeks. Then we applied a genome wide cDNA microarray technology to analyze genes expressed in femoral head of two groups and also serum levels of cholesterol (TC) were measured in the two groups. Results (1) There were a total of 111 expression genes which were changed by a minimum of two-fold and also it was found that 18 pathways had significant changes in these differential genes by molecule annotation system (MAS) analysis in femoral head of model group compared with normal rats. (2) There were 6 upregulated genes related to fatty acid metabolism (FAM) pathway ( Acadl, Cpt2, Acaa2, Acat1, Acsl1, Hadhb ), 2 upregulated genes related to fatty acid elongation in mitochondria (FAEM) ( Acaa2, Hadhb ), 3 upregulated genes related to adipocytokine signaling pathway (ACK) ( Cpt2, Prkaa2, Acsl1 ) et al in femoral head of model group compared with normal rats. (3) Serum levels of cholesterol significantly increased 21.2% in the model group compared with the normal group (1.754 ± 0.264 mol/L vs 1.447 ± 0.142 mol/L, p Conclusions The data suggest that the upregulated genes related to fat metabolism in the pathways of femoral head of steroid-induced osteonecrotic rats might play an important role in promoting the synthesis of fatty acid and cholesterol and fat metabolism could be mediated by FAM, FAEM and ACK pathways. The changes of multiple gene expression and numerous pathways could play major roles in steroid-induced osteonecrosis pathogenesis. (This study was supported by National Natural Science Foundation of China, NSFC 30472173).