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

Hui Sheng,Wing Cheung,Yi Wang,Ge Zhang,Kwong Lee,Chun Chan,Ling Qin,Kwok Leung,Hong Wang

doi:10.1186/1749-799x-2-15

Hui Sheng, Wing Cheung + Show 7 more

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https://doi.org/10.1186/1749-799x-2-15

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Abstract

BackgroundIncreased 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.ObjectiveThe present study was designed to test the hypothesis that there might be a close association between elevated adipogenesis and steroid-associated ON development.MethodsON 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).ResultsLocal 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.ConclusionThese findings support our hypothesis that there is a close association between elevated adipogenesis and steroid-associated osteonecrosis development.

Highlights

Increased bone marrow lipid deposition in steroid-associated osteonecrosis (ON) implies that abnormalities in fat metabolism play an important role in ON development
The adipogenic differentiation ability of mesenchymal stem cells (MSCs) and PPARγ2 expression in either ON+ or MON group were elevated significantly as compared with either ON- or SON group. These findings support our hypothesis that there is a close association between elevated adipogenesis and steroidassociated osteonecrosis development
One possibility is that marrow lipid was a consequence of the adipogenesis of marrow mesenchymal stem cells (MSCs) [7]

Summary

Introduction

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). It remains unclear whether there is a close association between elevated adipogenesis and steroid-associated ON development. One possibility is that marrow lipid was a consequence of the adipogenesis of marrow mesenchymal stem cells (MSCs) [7]. Results of a previous study showed increased number of small size fat cells in the early steroid-associated ON, that might be derived from the adipogenic differentiation of MSCs [8]. The relationship between the adipogenesis of marrow MSCs and steroid-associated ON remains unclear. The present study was designed to compare the adipogenesis of MSCs between rabbits with ON and rabbits without ON, rabbits with single ON lesion and rabbits with multiple ON lesions using our established experimental model [11]

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Conclusion