Relationship of age and body mass index to the expression of obesity and osteoarthritis related genes in human meniscus

OBJECTIVE: Aging and obesity contribute to the initiation and progression of osteoarthritis with little information on their relation to gene expression in joint tissues, particularly the meniscus. Here, we test the hypothesis that patient age and body mass index (BMI) correlate with the expression of osteoarthritis- and obesity-related gene signatures in the meniscus. DESIGN: Meniscus was obtained from patients (N=68) undergoing arthroscopic partial meniscectomy. The mRNA expression of twenty-four osteoarthritis-related and four obesity-related genes in meniscus was assessed by qRT-PCR. The relationship between gene expression and patient age and BMI was analyzed using Spearman’s rank-order correlation. Hierarchical cluster dendrogram and heat maps were generated to study inter-gene associations. RESULTS: Age was negatively correlated (P<0.05) with the expression of MMP-1 (r=−0.447), NFκB2 (r=−0.361), NFκBIA (r=−0.312), IκBA (r=−0.308), IL-8 (r=−0.305), ADAMTS-4 (r=−0.294), APLN (r=−0.250) and IL-6 (r=−0.244). Likewise, BMI was negatively correlated with the expression of APLN (r=−0.328), ACAN (r=−0.268) and MMP-1 (r=−0.261). After adjusting for the correlation between age and BMI (r=0.310; P=0.008), the only independent effect of BMI on gene expression was for APLN (r=−0.272). However, age had an independent effect on expression on ADAMTS-4 (r=−0.253), MMP-1 (r=−0.399), IL-8 (r=−0.327), COL1A1 (r=−0.287), NFκBIA (r=−0.278), NFκB2 (r=−0.312) and IκBA (r=−0.299). The gene-correlation analysis identified four clusters of potentially relevant genes: transcription factors, matrix degrading enzymes, cytokines and chemokines, and obesity genes. CONCLUSION: Age and BMI were negatively correlated with several osteoarthritis- and obesity-related genes. While the bulk of these changes appeared to be driven by age, expression of APLN was related to BMI. Inter-gene correlations implicated a common regulatory role of strongly correlated genes. Although age-related variations in gene expression are potentially more pertinent than obesity-related differences for the role of the meniscus in osteoarthritis development, further investigation into the role of APLN in meniscus and joint health is warranted.