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

年龄对ADAM8失活小鼠椎间盘组织形态和基因表达的影响

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Abstract

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.

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