Expression of degenerative markers in intervertebral discs of young and elderly asymptomatic individuals

Abstract

Intervertebral disc (IVD) degeneration is a remodeling process mediated by several growth factors and cytokines. This process has been extensively studied in vitro and with pathologic specimens obtained during surgery for scoliosis or back pain. However, the occurrence and temporal evolution of these molecules during normal aging, particularly in the cervical segment, is not known. Our objective was to study and compare the presence of putative mediators in the IVD of young (<35 years, G1) and elderly (>65 years, G2) presumably asymptomatic individuals. Thirty C4-5 and C5-6 discs and thirty L4-5 and L5-S1 discs per group were collected during the autopsy of individuals whose family members denied a history of neck or back pain. Discs were divided into anterior, central (lumbar only) and posterior sectors for analysis. Immunohistochemistry for TNF-α, IL-1β, VEGF, NGF-β, BDNF, TIMP-1, MMP-1, -2 and -3 was performed and reactivity compared between groups and sectors. All of these molecules were detected in every disc sector of both G1 and G2. Most statistical comparisons (25/45, 55.6%) revealed an increase in mediator expression in G2 in relation to G1. Regional differences in the expression of remodeling enzymes were rare; NGF-β and BDNF had slightly higher expression in the cervical segment of elderly individuals. A senescent profile with elevated VEGF, MMP-2 and MMP-3 was observed across most G2 disc regions and were generally elevated from G1. In conclusion, the mere presence of any of the studied molecules inside the IVD cannot be considered pathologic. Expression of remodeling enzymes and inflammatory mediators is relatively similar across different vertebral segments and disc regions leading to a common degenerated pattern, while neurotrophins have slightly higher expression in cervical discs. These findings support the concept that disc remodeling in different segments follows a similar pathway that can be potentially mediated to avoid structural failure.

Fig 1. IHC staining, G1 specimens.

Disc region and Thompson grade (Th) included. Reactivity was mostly intracellular but occasional ECM reactivity is shown. The asterisk denotes a fissure. Scale bar applies to all figures.

Fig 2. IHC staining, G2 specimens.

Disc region and Thompson grade (Th) included. Reactivity is enhanced when compared to G1 specimens but the localization pattern was similar. Sporadic ECM reactivity is also found (IL-1β, BDNF). Groups of chondrocytes usually had a similar expression pattern (MMP-1, TNF-α). Scale bar applies to all figures.

Fig 3. Expression of studied markers per disc region and vertebral segment.

Error bars represent standard error of the mean. Asterisks mark statistical significance at .05 level for the G1 versus G2 comparison.