Elevated adipogenesis of marrow mesenchymal stem cells during early steroid-associated osteonecrosis development.
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 (PPARgamma2). 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 PPARgamma2 expression in either ON+ or MON group were elevated significantly as compared with either ON- or SON group.


CONCLUSIONS
These findings support our hypothesis that there is a close association between elevated adipogenesis and steroid-associated osteonecrosis development.
Sheng
Hui H
HH
Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
Zhang
Ge G
GG
Cheung
Wing Hoi Wh
WH
Chan
Chun Wai Cw
CW
Wang
Yi Xiang Yx
YX
Lee
Kwong Man Km
KM
Wang
Hong Fu Hf
HF
Leung
Kwok Sui Ks
KS
Qin
Ling L
LL