Elevated adipogenesis of marrow mesenchymal stem cells during early steroid-associated osteonecrosis development

Abstract Background Increased bone marrow lipid deposition in steroid-associated osteonecrosis (ON) implies that abnormalities in fat metabolism play an important role in ON development. The increase in lipid deposition might be explained by elevated adipogenesis of marrow mesenchymal stem cells (MSCs). However, it remains unclear whether there is a close association between elevated adipogenesis and steroid-associated ON development. Objective The present study was designed to test the hypothesis that there might be a close association between elevated adipogenesis and steroid-associated ON development. Methods ON rabbit model was induced based on our established protocol. Dynamic-MRI was employed for local intra-osseous perfusion evaluation in bilateral femora. Two weeks after induction, bone marrow was harvested for evaluating the ability of adipogenic differentiation of marrow MSCs at both cellular and mRNA level involving adipogenesis-related gene peroxisome proliferator-activated receptor gamma2 (PPARγ2). The bilateral femora were dissected for examining marrow lipid deposition by quantifying fat cell number, fat cell size, lipid deposition area and ON lesions. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON occurrence, the rabbits were divided into ON + (with at least one ON lesion) group and ON - (without ON lesion) group. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON extension, the ON + rabbits were further divided into sub-single-lesion group (SON group: with one ON lesion) and sub-multiple-lesion group (MON group: with more than one ON lesion). Results Local intra-osseous perfusion index was found lower in either ON + or MON group when compared to either ON - or SON group, whereas the marrow fat cells number and area were much larger in either ON + or MON group as compared with ON - and SON group. The adipogenic differentiation ability of MSCs and PPARγ2 expression in either ON + or MON group were elevated significantly as compared with either ON - or SON group. Conclusion These findings support our hypothesis that there is a close association between elevated adipogenesis and steroid-associated osteonecrosis development.