Little is known about gene expression in meniscal tears, particularly in relation to injury pattern and patient age and sex. The purpose of this study was to test the hypothesis that gene expression in meniscal tears varies depending on patient age and sex and whether the anterior cruciate ligament (ACL) is also torn.
Methods: Meniscal tissue from twenty-eight patients with an
isolated meniscal tear or a meniscal tear with a concomitant ACL tear was collected at the time of clinically indicated partial meniscectomy. Messenger GSK923295 order RNA (mRNA) expression was examined by quantitative real-time polymerase chain reaction for molecular markers of osteoarthritis including proinflammatory cytokines (interleukin [IL]-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor-alpha [TNF alpha]), chemokines (IL-8, CCL3, CCL3L1, CXCL1, CXCL3, CXCL6, and CCL20), aggrecanases (ADAMTS-4 [a disintegrin and metalloproteinase with thrombospondin type-4 motifs] and ADAMTS-5), matrix metalloproteinases (MMP-1, MMP-3, MMP-9, and MMP-13), transcription factors (NF kappa
B2 [nuclear factor kappa B2], NF kappa BIA [NF-kappa B inhibitor alpha], and I kappa BA [inhibitor of kappa B alpha]), and matrix components (bone morphogenetic protein [BMP]-2, type-I collagen alpha 1 [Col1a1], Col2a1, and aggrecan).
Results: Expression of IL-1 beta (p = 0.02), ADAMTS-5 (p = 0.001), MMP-1 (p = 0.007), MMP-9 (p = 0.002), MMP-13 (p = 0.01), and NF kappa C59 supplier selleck products B2 (p = 0.01) was significantly higher in patients with a meniscal tear who were under the age of forty years than it was in those over the age
of forty years. Similarly, the expression of ADAMTS-4 (p = 0.002), ADAMTS-5 (p = 0.02), MMP-1 (p = 0.02), and MMP-13 (p = 0.0002) was higher in patients with a meniscal tear and an ACL tear who were under the age of forty years than it was in those over forty years. In patients with a meniscal tear and an ACL tear, the expression of IL-1 beta (p = 0.01), TNF alpha (p = 0.02), MMP-13 (p = 0.004), CCL3 (p = 0.03), and CCL3L1 (p = 0.03) was significantly higher, while that of aggrecan (p = 0.03) was lower, than that in patients with a meniscal tear alone. The only sex-based difference in gene expression was higher levels of CCL3L1 in female patients (p < 0.05) of all ages with combined injuries.
Conclusions and Clinical Relevance: These findings suggest clinically relevant differences in the response of the knee to meniscal tears on the basis of patient age and sex. Elevated expression levels of arthritis-related markers indicate an increased catabolic response in patients under forty years old. Higher expression of catabolic markers in patients with meniscal and ACL tears suggests this combined injury pattern is more likely to lead to the development of osteoarthritis.