Comparative Analysis of Gene Expression between Cartilage and Menisci in Early-Phase Osteoarthritis of the Knee-An Animal Model Study

摘要

Cartilage degeneration is believed to be the primary event in the development of osteoarthritis (OA). On the other hand, meniscal degeneration is observed with high prevalence, and some researchers have pointed out that pathological changes in menisci precede that of cartilage. The purpose of the present study is to investigate comprehensive gene expression pattern of cartilage and menisci in the initial phase of surgically induced OA and to compare them. Secondary OA was surgically induced in 10-week-old male Wistar rats by anterior cruciate ligament transection (ACLT). Articular cartilage and menisci were separately dissected from six ACLT- and six sham-operated rats. Each specimen was analyzed by microarray, histological, and immunohistochemical analysis 3 weeks after surgery. Of the 36,685 transcripts detectable by microarray, the number of upregulated transcripts in ACLT menisci was 2.5-fold compared with that in ACLT menisci in any given threshold. Cluster analysis using the Database for Annotation Visualization and Integrated Discovery (DAVID) showed genes related to OA, such as response to stimulus, angiogenesis, and apoptosis, which were predominantly found in menisci in ACLT rats. Representative proteases including Adamts2, 4, Mmp2, 12, 13, 14, 16, extracellular matrix genes including versican (Vcan), lumican (Lum), syndecan1 (Sdc1), and Prostaglandin endoperoxide synthase2 (Ptgs2) were up-regulated in menisci, but were not up-regulated in cartilage. Our results indicated that the molecular changes that occurred in menisci preceded those occurred in cartilage in the very early phase of surgically induced OA models.