Distinct adhesion energy and extracellular matrix profiles of healthy and osteoarthritic human chondrocytes

Osteoarthritis (OA) is a common degenerative joint disease characterized by the progressive degeneration of articular cartilage (AC), resulting in pain, stiffness, and reduced joint function. Despite its widespread prevalence, effective treatments for OA remain elusive, partly due to challenges in accurately modeling the disease. In the present study, adhesion energy, collagen (COL), and total glycosaminoglycans (GAG), the main extracellular matrix (ECM) components of AC, and their potential correlations were evaluated in human chondrocytes derived from both healthy and OA male donors. A model surface of silicon nitride was used to investigate adhesion energy using atomic force microscopy (AFM), while colorimetric assays were applied to quantify COL and GAG at five different time points during monoculture (days 0, 1, 7, 14, and 21). Our results indicate significant heterogeneity in adhesion energies at both donor and phenotype levels. Chondrocytes isolated from healthy donors consistently display higher adhesion energies, along with greater heterogeneity, compared to those derived from OA donors. These differences in adhesion energy and heterogeneity can be attributed to greater diversity and density of cellular surface molecules in cells from healthy donors. In contrast, total GAG and COL levels were significantly elevated in OA chondrocytes compared to those in healthy chondrocytes. Moreover, the study found a positive correlation between adhesion energy and GAG production in OA-derived chondrocytes, but no significant correlations with DNA or COL levels. No correlation was observed between adhesion energy and GAG, DNA, or COL levels in healthy cells. In conclusion, these findings highlight the importance of considering individual donor characteristics when developing OA disease models, therapeutics, or engineered tissues.