Ischaemic injury to femoral head induces apoptotic and oncotic cell death.
OBJECTIVE
The mechanism of cell death in ischaemic osteonecrosis of the femoral head is not clear. Therefore, this study was designed to clarify the mode of cell death following ischaemic osteonecrosis of the femoral head in an established pig model.


METHODS
Morphological assessment, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) assay, detection of DNA laddering and transmission electron microscopy studies were performed to determine whether apoptosis is one of the pathways of cell death following ischaemic osteonecrosis of the femoral head.


RESULTS
Mode of cell death was investigated from 2 to 14 days following the surgical induction of ischaemia. Ischaemic femoral heads showed morphological evidence of cell death by oncotic and apoptotic pathways in earlier stages of osteonecrosis. TUNEL positive cells were seen from 2 to 14 days following the induction of ischaemia. DNA samples obtained from ischaemic femoral heads following the induction of ischaemia showed nucleosomal ladders indicating apoptotic cell death. Electron micrographs also showed morphological changes associated with apoptosis.


CONCLUSIONS
This study demonstrates that oncosis is not the sole mechanism of cell death following ischaemic injury of the femoral head. Both apoptosis and oncosis are involved as a result of ischaemic injury to the femoral head.
Kothapalli
Ravi
R
Center for Research in Skeletal Development and Pediatric Orthopaedics, Shriners Hospital for Children, Tampa, Florida 33612, USA.
Aya-ay
James P
JP
Bian
Haikuo
H
Garces
Amanda
A
Kim
Harry K W
HK
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053938:DNA Fragmentation; D005269:Femur / Q000098:blood supply / Q000473:pathology*; D005271:Femur Head Necrosis / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000473:pathology*; D008297:Male; D013552:Swine