Osteoarthritis is a painful, age-related joint disease in which cellular senescence plays a central role. Senescent cells are retained from the active cell cycle and secrete harmful factors that contribute to cartilage degradation and tissue damage. Transcriptomic analysis of cartilage and blood samples from osteoarthritis patients revealed two distinct gene expression profiles, offering opportunities for clinical stratification and personalized treatment approaches.
To investigate disease mechanisms, human bone–cartilage models exhibiting senescent features were developed. Mechanical loading, ionizing radiation, and their combination were applied to generate three experimental conditions. Loading primarily induced inflammatory responses, radiation suppressed cell proliferation, and the combination produced a fully senescent phenotype. High-resolution 3D synchrotron imaging further demonstrated that irradiation to loading could mitigate the deleterious effects of...
Show moreOsteoarthritis is a painful, age-related joint disease in which cellular senescence plays a central role. Senescent cells are retained from the active cell cycle and secrete harmful factors that contribute to cartilage degradation and tissue damage. Transcriptomic analysis of cartilage and blood samples from osteoarthritis patients revealed two distinct gene expression profiles, offering opportunities for clinical stratification and personalized treatment approaches.
To investigate disease mechanisms, human bone–cartilage models exhibiting senescent features were developed. Mechanical loading, ionizing radiation, and their combination were applied to generate three experimental conditions. Loading primarily induced inflammatory responses, radiation suppressed cell proliferation, and the combination produced a fully senescent phenotype. High-resolution 3D synchrotron imaging further demonstrated that irradiation to loading could mitigate the deleterious effects of subsequent mechanical loading.
The utility of these models was tested with potential anti-senescent compounds, which reduced the senescent phenotype, supporting their application in early drug screening. A two-step strategy is proposed: preliminary testing in organoid-based in vitro systems followed by validation in the bone–cartilage model, enabling efficient selection of promising therapeutic agents.
Finally, innovative platforms such as joint-on-a-chip technology were explored. By incorporating patient-derived cells, these systems allow individualized drug response testing and pave the way for precision therapies against osteoarthritis.
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