Gene Expression in Meniscal Tears at the Time of Arthroscopic Partial Meniscectomy Predicts the Progression of Osteoarthritis Within 6 Years of Surgery

Abstract

Background: While knees with meniscal tears are associated with a heightened risk of developing osteoarthritis (OA), it is difficult to predict which patients are at the greatest risk for OA. Gene signatures in menisci that are resected during arthroscopic partial meniscectomy (APM) may provide insight into the risk of OA progression.

Hypothesis: Meniscal gene signatures at the time of APM will predict radiographic OA progression.

Study design: Case series; Level of evidence, 4.

Methods: Meniscal fragments were collected from 38 patients without OA during clinically indicated APM of the medial meniscus. The expression of 28 candidate genes with known roles in cartilage homeostasis, OA, extracellular matrix degradation, and obesity was assessed by quantitative real-time polymerase chain reaction. Weightbearing radiographs obtained before surgery and at final follow-up were graded by a musculoskeletal radiologist using the Kellgren-Lawrence classification of OA. The association of meniscal gene expression at baseline with the progression of radiographic OA was determined.

Results: Gene expression and baseline and follow-up radiographic data were available from 31 patients (81.6%) at a mean follow-up of 6.2 ± 1.3 years. Patients without OA progression had significantly higher expression of 7 genes: MMP9 (5.1-fold; P = .002), IL8 (2.9-fold; P = .016), CCL3 (3.7-fold; P = .032), CCL3L1 (4.5-fold; P = .008), CXCL6 (6.2-fold; P = .010), LEP (5.2-fold; P = .004), and RETN (46-fold; P = .008).

Conclusion: Gene expression in the meniscus at the time of APM may be associated with the risk for progression of OA after surgery. Elevated expression of the aforementioned genes may reflect a chondroprotective response. Stratifying the risk for OA progression after APM could facilitate targeted interventions to delay or prevent the development of OA. Further studies in a larger cohort with an extended follow-up, and inclusion of additional genes, are warranted to better characterize this association.

Keywords: gene expression; meniscal tear; meniscectomy; osteoarthritis.

Figure 1.

Gene transcripts differentially expressed between patients who showed radiographic osteoarthritis (OA) progression at follow-up (“Some”) and those who did not (“No”).

Figure 2.

Gene transcripts differentially expressed across patients with different categories of radiographic osteoarthritis (OA) progression (Kellgren-Lawrence grades: I [minimal], II [mild], III [moderate], IV [severe]) at follow-up based on knee compartment and rate of progression. Label a indicates a significant difference between 2 groups (P < .05). Similarly, label b indicates a significant difference between 2 groups (P < .05).