Osteoarthritis – the entire joint disease

Abstract

Pertinent literature suggests that osteoarthritis (OA) emanates from the dysfunction of the whole joint, affecting the articular cartilage, synovium, and subchondral bone, the tissues revealing anatomical and molecular interactions. The study aimed to explore a spectrum of the structural joint damage characteristic of OA employing morphology methods. The entire joint tissues collected from 54 OA subjects (mean age 69 (range 35–85 years)) who underwent joint replacement surgery were processed and used in the study. Toluidine blue, Safranin O/Fast green, and Sirius red staining were used to detect proteoglycans, glycosaminoglycans, and collagen content of the articular cartilage. Synovitis was assessed using CD45, CD14, and CD68 (macrophages), CD45, and CD19 (B lymphocytes), CD45, CD3, CD4 (T lymphocytes), tumor necrosis factor alpha (TNF-α). Synovial fibroblasts were characterized by the expression of CD31, CD34, podoplanin (PDPN), and α-smooth muscle actin (α-SMA). Synovial histopathology was evaluated according to Krenn and Morawietz scores. Statistical data analysis and plotting were performed using Prism 9 and JMP Pro 16 software. Degradation of cartilage and changes in the proteoglycan and collagen content were confirmed using histochemical markers. Hypertrophic chondrocytes with abundant cytoplasmic inclusions, deep vascular invasions into the cartilage matrix, and reactive chondroclasts were evident. A median synovitis score was 2 (IQR 1–4). The synovial lesions consistent with low-grade synovitis demonstrated an increase in thickness of the lining layer (CD45/CD14/CD68 and CD31/CD34/PDPN positivity) and stromal cellularity (with CD68/ TNF-α positivity), the presence of a few, mostly perivascular CD45+/ CD3+/CD4+ lymphocytes. Loss of articular cartilage structure and function, and its remodeling is one of the major hallmarks of OA. Apart from the cartilage damage, synovial low-grade inflammation over time, or through injury, sustained during the life course has a strong cumulative impact and contributes to progressive OA-associated joint de struction.