The relationship between apoptosis of endplate chondrocytes and aging and degeneration of the intervertebral disc.

Abstract

Apoptosis in cervical intervertebral disc cells and cartilaginous endplate cells was examined by the nick end labeling (TUNEL) technique during the process of natural aging and in a mouse experimental spondylosis model. To determine the role of apoptosis in aging and degeneration of intervertebral discs by monitoring chronologic changes in the quantity and localization of apoptotic cells. Apoptosis occurs within human intervertebral discs, but little is known about the pathologic significance of this process. On the other hand, the cartilaginous endplate is known to decrease in thickness and to disappear with aging and degeneration. The cause of this age-related change remains unclear. A mouse spondylosis model was prepared via surgical resection of the posterior spinal element in 12 mice to examine the experimentally induced spondylosis process. Eighteen naturally aged mice were also used to examine the influence of aging. Paraffin-embedded midsagittal sections of the cervical spine were obtained 2, 3, 6, and 12 months after surgery in the spondylosis model and in the age-matched naturally aged mice, as well as in 4-week-old and 18-month-old naturally aged mice. Sections were stained with hematoxylin and eosin, safranin-O, and the TUNEL procedure. The number of apoptotic cells and vital cells were counted in the cartilaginous endplate of the intervertebral disc excluding the growth cartilage, and the degree of disappearance of the cartilaginous endplate was evaluated. Apoptosis, particularly noticeable in the cartilaginous endplate, increased with age and resulted in a marked decrease in cell density. Subsequently, the structure of the cartilaginous endplate began to disappear. Apoptosis was more evident and the structure of the cartilaginous endplate began to disappear more rapidly in the surgically treated group than in the naturally aged group. TUNEL-positive cells in the cartilaginous endplate increased with age, with destruction of the cartilaginous endplate after apoptosis (TUNEL-positive cell death). The application of the spondylosis model increased the incidence of apoptosis preceding the development of spondylosis. This suggests that apoptosis plays a role in the age-related changes seen in the cartilaginous endplate of the intervertebral disc and in the experimentally induced spondylosis process.