APOPTOSIS OF CELLS OF NUCLEUS PULPOSUS AND ACTIVATION MECHANISM OF INTERCELLULAR SIGNALING DURING DEGENERATION OF INTERVERTEBRAL DISC

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We previously conducted immunohistological studies of changes in TGF-β and BMP expression in nucleus pulposus cells following degeneration of the intervertebral disc. These studies suggested that changes in TGF-β expression are associated with apoptosis of cells. Following this finding, the present study was undertaken to clarify the mechanism of aging from the viewpoint of apoptosis, using molecular biological methods. The study involved a senescence-accelerated mouse strain (SAM-P/6) as the animal model, allowing observation of aging in a short time period. During last year, we removed the intervertebral discs of the cervical spine from male senescence-accelerated mice at ages 4, 8, 12, 16, 20, 24, 28, 32 and 50 weeks and examined immunohistologically the expression of TGF-β1, -β2, -β3 and their receptors in the discs' nucleus pulposus cells. The study revealed that as age advanced the expression of nucleus pulposus cell TGF-β1, -β2, -β3 and their receptors decreased, reaching almost … More zero at age 50 weeks and was accompanied by a decrease in the number of nucleus pulposus cells. This year, we conducted an experiment designed to demonstrate that such a decrease in nucleus pulposus cells is due to apoptosis. In this study, nucleus pulp cells of senescence-accelerated mice were stained positively using the TUNEL method and were found to already have caspase activity at age 32 weeks, suggesting that apoptosis had begun at this age. Morphological observation of the nuclei of the cells with an electron microscope also revealed apoptotic changes. The changes suggesting apoptosis were more marked at age 50 weeks.In 2003, we conducted immunohistological studies of ASK1, JNK and p38 aimed at clarifying the mechanism for intracellular signal transduction associated with apoptosis during degeneration of intervertebral discs. As the disc degenerated, the expression of ASK1, JNK and p38 in nucleus pulposus cells was noted, but it was also observed in the control group. Thus, it was not possible to clarify the mechanism for intracellular signal transduction associated with apoptosis. Less