Effects of Age on Intervertebral Disc Tissue Morphology and Gene Expression in the ADAM8-Inactivation Mouse.

Purpose: To determine which age of mice should be used to compare the effects of ADAM8 mutation on intervertebral disc (IVD) responses to injury.

Methods

IVDs of ADAM8 mutant (Adam8EQ) and wild type (WT) mice, aged 3, 10 and 18 months were injured. IVD tissues were harvested 1 week post injury for histological and molecular studies.

Results

Histological scores increased with aging in intact IVDs, and there were no differences between Adam8EQ and WT mice (n = 11-28; p > 0.05). Safranin O-staining was less intense in 10-month than in 3-month-old mice, in both intact and injured IVDs (n = 3-15; p < 0.05). Cxcl1, Il6, and Adam8 gene expression levels were higher in the injured tail IVDs of 3-month-old Adam8EQ than WT mice (n = 18-30; p < 0.05); the injury-related differences diminished with increasing age.

Conclusions

No histological differences were found between Adam8EQ and WT mouse IVDs at 3, 10 or 18 months of age, in the intact or injured discs. The differences in inflammatory marker gene expression were detectable at age 3 months, but were less evident when the injury occurred at age 10 or 18 months. Therefore, to identify differences in injury responses between WT and Adam8EQ mouse IVDs, 3-month-old mice are superior to older mice.