Differential Expression of ACAN, COL1A1, and COL2A1 in Cartilage and Synovium During Osteoarthritis Progression: An Observational Pilot Study Supported by Preliminary Bioinformatic Analysis

Background: Osteoarthritis (OA) patients experience poorer quality of life due to persistent symptoms and chronic pain. Unfortunately, the molecular basis of OA development is poorly understood, thus posing a major challenge for therapeutic interventions. The aim of this study was to compare the expression of genes encoding key cartilage proteins in OA-affected tissue from the relatively preserved lateral compartment of the knee joint in relation to knee OA advancement stage. This study focuses on molecular changes in individual areas of the knee, which may be important for the use of partial endoprostheses in patients. Methods: This study included 31 patients with primary knee OA. OA-affected tissues (medial compartment of the knee joint) and tissues from the relatively preserved lateral compartment were collected from each patient. Gene expression was assessed by real-time polymerase chain reaction (PCR). A protein–protein interaction network and functional visualization were prepared. Results: Compared with the relatively preserved lateral compartment, the more severely OA-affected medial compartment demonstrated significantly higher COL1A1 mRNA expression in articular cartilage (p = 0.0045; Holm-adjusted p = 0.0269) and significantly higher ACAN mRNA expression in synovial tissue (p = 0.0091; Holm-adjusted p = 0.0458). In an exploratory subgroup analysis, patients with hypertension showed significantly higher COL1A1 mRNA expression in cartilage from the more severely OA-affected medial compartment than in the relatively preserved lateral compartment (p = 0.00054). The verified proteins were found to be associated with proteins involved in the cartilage development. Based on The Gene Expression Omnibus (GEO) database, late-OA chondrocytes presented higher ACAN and COL1A1, and lower collagen type II (COL2A1) mRNA expression than early-OA ones. In the synovium, late-OA tissue from the relatively preserved lateral compartment showed lower ACAN and higher COL1A1 mRNA expression than early-OA tissue. Conclusions: Numerous molecular changes are associated with OA. Cartilage and synovial membranes demonstrated similar changes in ACAN mRNA expression, whereas COL1A1 and COL2A1 displayed divergent expression patterns. The observed differences in gene expression depended on the part of tissue studied, biological features of patients and presence of comorbidities.