Differential Biological and Molecular Profiling of Mesenchymal Progenitor Cells in Cartilage from Osteoarthritis and...

Mesenchymal progenitor cells (MPCs) play a significant role in articular cartilage homeostasis and regeneration. Yet, the functional dynamics and molecular characteristics of MPCs may differ significantly across various pathological conditions. Hence, this study comprehensively investigates the biological and molecular characteristics of MPCs isolated from articular cartilage of patients with osteoarthritis (OA) and rheumatoid arthritis (RA), aiming to uncover disease-specific differences that could offer insights into targeted regenerative therapies. Using flow cytometry, gene expression analysis, and in vitro differentiation assays, we assessed the phenotype, growth potential, senescence, cytogenetic instability, and chondrogenic potential to delineate molecular pathways uniquely active in each disease context. Phenotypically, both OA and RA-MPCs retained markers of mesenchymal stem cells (MSCs), but OA-derived MPCs exhibited higher fold expression of progenitor markers (OCT-4, NANOG, SOX-2, and SSEA-4), suggesting a more activated state. Functionally, OA-MPCs demonstrated increased growth kinetics (higher proliferation rate and decreased population doubling time) with a significant shift towards adipogenic lineages (increased fold expression of LPL, AP2, and PPAR-γ). However, there were no differences in the osteogenic and chondrogenic potential. Gene expression analysis revealed upregulation of genes involved in extracellular matrix production and cartilage development (COL2-α1, ACAN, FGFR3, TGF-β3, ANXA6, CNTN1, MATN1, TGF-β1, VIM, and SOX9) in 3D cultures compared with 2D or monolayer cultures. Collectively, these findings demonstrate that, while multipotent MPCs are present in both OA and RA articular cartilage, they can exhibit fundamentally altered biological behaviors and molecular signatures reflective of the local disease microenvironment. Understanding these differences is critical for optimizing cell-based therapeutic strategies tailored to each condition and may facilitate the development of novel interventions targeting endogenous progenitor cells for cartilage repair.