Continuous occurrence of both insufficient neovascularization and elevated vascular permeability in rabbit proximal femur during inadequate repair of steroid-associated osteonecrotic lesions.
OBJECTIVE
To examine the features of the intraosseous vasculature, the size of the marrow stem cell pool (MSCP), and expression of vascular endothelial growth factor A (VEGF) during inadequate repair of steroid-associated osteonecrotic lesions in rabbits.


METHODS
Steroid-associated osteonecrosis was induced in male rabbits. At 0, 1, 2, 4, and 6 weeks postinduction, vascularization and permeability indices were quantified by dynamic magnetic resonance imaging (MRI). In addition, the size of the MSCP in the hematopoietic and mesenchymal compartments was determined, and marrow mononuclear cells expressing specific surface markers for endothelial progenitor cells or periendothelial mural precursor cells were counted. At various time points after the rabbits were killed, the proximal femora were dissected to examine the intraosseous vasculature by angiography, histomorphometry, and ultramorphology. In addition, osteonecrotic lesion repair and marrow VEGF expression were evaluated.


RESULTS
Lesion formation without repair was observed at 2 weeks after induction of steroid-associated osteonecrosis. Rabbits displaying destructive repair (DR+) and those displaying reparative osteogenesis (DR-) from 4 weeks to 6 weeks postinduction were identified. From week 2 to week 6, the vascularization index was significantly lower in DR+ rabbits compared with DR- rabbits, whereas the permeability index was significantly higher in DR+ rabbits compared with DR- rabbits. The features of the intraosseous vasculature determined by angiography, histomorphometry, and ultramorphology were consistent with those determined by dynamic MRI. The MSCP size and number of marrow mononuclear cells expressing specific surface markers were all significantly lower in DR+ rabbits than in DR- rabbits from week 1 to week 6. The increased VEGF expression at 2 weeks was maintained through week 6 in DR+ rabbits, whereas VEGF expression decreased in DR- rabbits from week 2 to week 6.


CONCLUSIONS
Continuous occurrence of both insufficient neovascularization and elevated vascular permeability is accompanied by a continuously low- level MSCP and uncontrolled VEGF expression during inadequate repair of steroid-associated osteonecrotic lesions.
Zhang
Ge
G
Chinese University of Hong Kong, Hong Kong, China.
Sheng
Hui
H
He
Yi-Xin
YX
Xie
Xin-Hui
XH
Wang
Yi-Xiang
YX
Lee
Kwong-Man
KM
Yeung
Ka-Wai
KW
Li
Zi-Rong
ZR
He
Wei
W
Griffith
James F
JF
Leung
Kwok-Sui
KS
Qin
Ling
L
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002199:Capillary Permeability / Q000502:physiology*; D004195:Disease Models, Animal; D005269:Femur / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D010012:Osteogenesis / Q000502:physiology; D010020:Osteonecrosis / Q000473:pathology / Q000503:physiopathology*; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000473:pathology; D013256:Steroids / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D013256:Steroids; D042461:Vascular Endothelial Growth Factor A