Caspase-3

Post-traumatic caspase-3 expression in the adjacent areas of growth plate injury site: a morphological study.

" The objective of this study was to determine the impact of an injury in the growth plate chondrocytes through the analyses of the caspase-3 and cleaved PARP-1, and levels of the inflammatory cytokines, Interleukin-6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α), in order to acquire more information about post-injury reactions of physeal cell turnover. In experimental bones, neo-formed bone trabeculae-resulting from bone formation repair-invaded the growth plate and reached the metaphyseal bone tissue (bone bridge), and this could result in some growth arrest. We demonstrated increased expression levels of the inflammatory cytokines IL-6 and TNF-α.  Analyses of the caspase-3 and cleaved PARP-1 showed that the physeal apoptosis rate of the experimental bones was significantly higher than that of the control ones. The inflammation process causes stress to chondrocytes that will die as a biological defense mechanism, and will also increase the survival of new chondrocytes for maintaining cell homeostasis. "

"bone bridge formation does not involve endochondral ossification"

"In experimental rats, the area of the injury was first infiltrated with inflammatory cells and some cellular debris and subsequently occupied by marrow-derived fibroblast-like mesenchymal cells and characterized by hypervascularity"

"In lateral areas, adjacent to the forming bone bridge, endochondral osteogenesis in the metaphysis is evident"

Caspase-3 expression increased over 30 days after growth plate injury.  IL-6 levels peaked 8 hours after injury and tended to decrease.  TNF-a levels had multiple peaks at both 1 and 30 days.

"Initiator caspases (caspases 2, 8, 9, and 10) are activated through the apoptosis-signaling pathways and activate the effector caspases (caspases 3, 6, and 7), which, in an expanding cascade, carry out apoptosis"

"PARP-1 is a nuclear DNA repair enzyme that is implicated in DNA repair and maintenance of genomic integrity. Caspase-mediated processing of PARP-1 effectively results in potent and irreversible inactivation of the protein. In apoptosis, PARP-1 is cleaved by activated caspase-3 between Asp214 and Gly215, resulting in the formation of an N-terminal 24 kDa fragment containing most of the DNA binding domain and a C-terminal 89 kDa fragment containing the catalytic domain. Inactivation of PARP-1 will result in the prevention of NAD+ depletion caused by PARP-1 activation. So, the proteolysis of PARP-1 renders the enzyme inactive and this further facilitates apoptotic cell death."

Cleaved PARP-1 increased over time in growth plate injury.