The intervertebral disc from embryonic development to disc degeneration: insights into spatial cellular organization

Abstract

Background context: Low back pain is commonly attributed to intervertebral disc (IVD) degeneration. IVD resembles articular cartilage in its biochemical and cellular composition in many ways. For articular cartilage, degeneration stage-specific characteristic spatial chondrocyte patterns have recently been described.

Purpose: This study addresses how spatial chondrocyte organization in the IVD changes from early embryonic development to end stage degeneration.

Study design: Ex vivo immunohistochemical analysis.

Methods: We immunohistochemically investigated bovine IVD-tissue (n=72) from early embryonic development to early disc degeneration and human adult IVD-tissue (n=25) operated for trauma or degeneration for cellular density and chondrocyte spatial organization. IVD samples were sectioned along the main collagen fiber orientation. Nuclei were stained with DAPI and their number and spatial patterns were analyzed in an area of 250,000 µm² for each tissue category.

Results: The initially very high cellular density in the early embryonic bovine disc (11,431 cells/mm²) steadily decreases during gestation, growth and maturation to about 71 cell/mm² in the fully grown cattle. Interestingly, in human degenerative discs, a new increase in this figure could be noted (184 cells/mm). The IVD chondrocytes appear to be predominantly present as single cells. Especially in the time after birth, string-formations represent up to 32% of all cells in the anulus fibrosus, although single cells are the predominant spatial pattern (>50%) over the entire time. With increasing degeneration, the relative proportion of single cells in human IVDs continuously decreases (12%). At the same time, the share of cells organized in clusters increases (70%).

Conclusion: Similar to articular cartilage, spatial chondrocyte organization appears to be a strong indicator for local tissue degeneration in the IVD.

Clinical significance: In the future these findings may be important for the detection and therapy of IVD degeneration in early stages.

Keywords: Degeneration; Embryonic development; Intervertebral disc; Spatial organization.