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 (Adam8^EQ) 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 Adam8^EQ 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 Adam8^EQ than WT mice (n = 18-30; p < 0.05); the injury-related differences diminished with increasing age. Conclusions: No histological differences were found between Adam8^EQ 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 Adam8^EQ mouse IVDs, 3-month-old mice are superior to older mice.