Maturity-dependent cartilage cell plasticity and sensitivity to external perturbation. (June 2020) - Walsh, Shannon K.
Abstract: Objective: Articular cartilage undergoes biological and morphological changes throughout maturation. The prevalence of osteoarthritis in the aged population suggests that maturation predisposes cartilage to degradation and/or impaired regeneration, but this process is not fully understood. Therefore, the objective of this study was to characterize the cellular and genetic profile of cartilage, as well as biological plasticity in response to mechanical and culture time stimuli, as a function of animal maturity. Methods/design: Porcine articular cartilage explants were harvested from stifle joints of immature (2–4 weeks), adolescent (5–6 months), and mature (1–5 years) animals. Half of all samples were subjected to a single compressive mechanical load. Loaded samples were paired with unloaded controls for downstream analyses. Expression of cartilage progenitor cell markers CD105, CD44, and CD29 were determined via flow cytometry. Expression of matrix synthesis genes Col1, Col2, Col10, ACAN, and SOX9 were determined via qPCR. Tissue morphology and matrix content were examined histologically. Post-loading assays were performed immediately and following 7 days in culture. Results: CD105 and CD29 expression decreased with maturity, while CD44 expression was upregulated in cartilage from mature animals. Expression of matrix synthesis genes were generally upregulated in cartilage from mature animals, and adolescent animals showed the lowest expression of several matrix synthesizing genes. Culture time and mechanical loading analyses revealed greater plasticity to mechanical loading and culture time in cartilage from younger animals. Histology confirmed distinct structural and biochemical profiles across maturity. Conclusion: This study demonstrates differential, nonlinear expression of chondroprogenitor markers and matrix synthesis genes as a function of cartilage maturity, as well as loss of biological plasticity in aged tissue. These findings have likely implications for age-related loss of regeneration and osteoarthritis progression. Graphical abstract: Image 1 Highlights: Porcine cartilage was evaluated from immature, adolescent, and mature animals. Cartilage from immature animals had the highest plasticity to mechanical loading. Expression of progenitor markers CD105 and CD29 decreased with animal maturity. Adolescent animals had the lowest expression of several matrix synthesis genes.