Gene expression in meniscus tears at the time of arthroscopic partial meniscectomy predicts osteoarthritis progression

Abstract

Objectives:While meniscus tears are associated with an increased risk of developing knee osteoarthritis (OA), it is not possible to predict which patients are at the highest risk for developing OA. Gene signature in meniscus resected at the time of arthroscopic partial meniscectomy may provide insight into an individual’s risk of OA progression. The purpose of this study is to test the hypothesis that gene signatures at the time of arthroscopic partial meniscectomy predict radiographic progression of OA.Methods:Meniscus fragments were collected from 40 patients at the time of clinically indicated isolated arthroscopic partial medial meniscectomy. Gene expression was assessed by quantitative real-time PCR using a panel of 28 candidate genes with known roles in cartilage homeostasis, OA, extracellular-matrix degradation and obesity. Radiographs obtained prior to surgery and at final follow-up were graded by a musculoskeletal radiologist. The association of meniscus gene expression at the time of surgery with progression of radiographic OA was determined.Results:Gene expression in meniscus resected at arthroscopic partial medial meniscectomy and radiographic data at baseline and mean follow-up of 6.2 ± 1.3 years were available for 31 patients (77.5%). The cohort consisted of 45.2% females with a mean age of 48.5 ± 9.2 years and mean body mass index of 28.1 ± 5.1 kg/m2. Gene expression was associated with radiographic progression of OA (Table 1). Patients without OA progression had significantly higher expression of seven genes, namely MMP9 (5.1-fold, P=0.002), IL8 (2.9-fold, P=0.016), CCL3 (3.7-fold, P=0.032), CCL3L1 (4.5-fold, P=0.008), CXCL6 (6.2-fold, P=0.010), LEP (5.2-fold, P=0.004) and RETN (46-fold, P=0.008). Patients with progression showed very low expression of these genes (Figure 1). When segregating patients based on severity of OA progression, there was significantly increased expression of three genes (MMP9, CXCL6, LEP) among patients without any radiographic OA progression. There was an increased expression of CXCL6 (9.5-fold, P=0.042), LEP (4.3-fold, P=0.047) and MMP9 (5.0-fold, P=0.023) among those without any radiographic OA progression compared to those with rapid progression in the medial compartment. There was also an increased expression of MMP9 among patients without progression compared to those with progression in the lateral and/or patellofemoral compartments (7.2-fold, P=0.038).Conclusions:Our findings suggest that gene expression in the meniscus at the time of arthroscopic partial meniscectomy is associated with the risk for OA progression. Elevated expression of the aforementioned genes in non-progressors may reflect a potentially chondroprotective response. Further studies including additional genes, larger cohorts and extended follow-up are warranted to better characterize this association. Ultimately, this line of investigation could facilitate the development of more sensitive methods to determine the risk for OA progression among patients with meniscal injury and approaches to delay or prevent OA in this population.