Objectives: Despite clinical evidence demonstrating that meniscus tears are early events in the initiation and propagation of knee osteoarthritis (OA), the biology of how meniscus injury leads to changes in the articular cartilage is not well studied. Therefore, we compared the molecular biology of articular and meniscal cartilage within the same knees undergoing partial meniscectomy to advance our understanding of early molecular events in the knee that contribute to the development of OA following a meniscus tear. The purpose of this study was to test the hypothesis that meniscal and articular cartilage from knees undergoing arthroscopic partial meniscectomy will demonstrate molecular signature representative of early OA. Methods: Patients (n=12) with a known isolated medial meniscus tear without any knee chondrosis or radiographic OA were consented prior to surgery. During arthroscopic partial meniscectomy, a sample of their injured meniscus and a small fragment of their articular cartilage off the medial femoral condyle were procured. The transcriptome signatures measured through Affymetrix microarray were compared between the two tissues and underlying biological processes were explored computationally. Results: 3566 gene transcripts, representing several underlying biological processes, including extracellular matrix organization, wound healing, cell adhesion, chemotaxis, blood vessel morphogenesis, and angiogenesis, were differentially expressed between meniscus and articular cartilage. Conclusion: Articular cartilage and meniscus exhibit molecular events associated with OA at the time of partial meniscectomy despite no gross evidence of degeneration in the knee. These findings identify early effects of meniscus injury on meniscus and articular cartilage, which likely lead to the development of knee OA.