Analysis of Aging and Degeneration of the Human Intervertebral Disc: Comparison of Surgical Specimens With Normal Controls

Abstract

STUDY DESIGN: A prospective analysis of 33 control and 39 surgical human lumbar disc specimens from the anulus was undertaken to assess disc cell extracellular matrix production and cell function. The authors of this study analyzed immunohistochemical distributions of Types I, II, III and VI collagen, in situ localization of apoptotic disc cells, and tartrate-resistant acid phosphatase localization. OBJECTIVES: To quantify the incidence of apoptotic cell death in the anulus; examine the collagen distribution in the pericellular, territorial, and interterritorial matrix; examine matrix cell degeneration; and compare diseased tissue with normal tissue from control individuals. SUMMARY OF THE BACKGROUND DATA: Previous studies of disc histopathology have focused on extracellular matrix morphology and on biochemical synthetic and degenerative changes, but little is understood about the cell populations within the disc that are responsible for these changes. METHODS: In this study light microscopy, immunohistochemistry, enzyme histochemistry, and in situ hybridization were used to examine 33 patient and 39 control specimens of human anulus obtained either via surgical procedures or from donors to the Cooperative Human Tissue Network. RESULTS: The high incidence of apoptotic cell death was significantly greater in the control group (73.1 +/- 5.1% [mean +/- SEM]; n = 20) than among surgical specimens (53.5 +/- 5.6%; n = 20; P < 0.001); this was probably a result of the significantly greater average age in the control population (57.2 +/- 3.1 years) compared with that in the patient population (44.3 +/- 3.2 years; P < 0.001). Immunohistochemistry yielded findings that led to an expanded appreciation of the greatly modified extracellular domains that surrounded disc cells during aging and degeneration in both study groups. Enzyme histochemistry revealed the presence of tartrate-resistant acid phosphatase activity in human disc cells. CONCLUSIONS: These findings reveal that there is a high incidence of apoptosis in the intervertebral disc. Surviving cells are not synthetically inactive but are, rather, producing inappropriate matrix products during aging and degeneration. In certain instances it appears that the matrix surrounding the cell may form an isolation barrier, which may influence individual cell activity and intercellular communication. These results point to the need to 1) more fully understand the cause of disc cell death via apoptosis and to determine whether this programmed cell death can be reversed or halted, and 2) more fully understand the dynamic relation between disc cells and the surrounding extracellular matrix, which they produce and remodel. The factors regulating extracellular matrix-disc cell homeostasis in the disc are unknown, as is the relation between extracellular matrix and disc cell functional modulation. The morphologic findings of this study suggest that these issues are important considerations in disc cell biology. The identification of tartrate-resistant acid phosphatase activity in disc cells allows for a new area of study of disc extracellular matrix remodelling. In summary, these new perspectives provide new parameters with which to assess disc cell health and function.