Mechanobiology of the osteochondral unit using advanced imaging in preclinical osteoarthritis models

Traditional preclinical studies of osteoarthritis (OA) frequently rely on static, cross-sectional assessments that obscure the dynamic sequence of tissue compensation and failure. To capture the dynamic trajectory of OA and allow for the ready unravelling of any mechanoadaptive changes, an interpretive shift is required toward image-guided approaches that quantify temporal, spatial, and functional alterations. This review highlights how advanced 3D X-ray micro-computed tomography (microCT) has become a critical asset for exploring mechanisms driving joint pathology and pathomechanics in preclinical animal models. Temporally, longitudinal in vivo imaging allows direct tracking of joint malalignment and subchondral bone remodelling over time. The use of contrast agents permits imaging of articular cartilage, enabling the spatial evaluation of coordinated multi-tissue degeneration. Moreover, investigating the relationship between structural changes and functional alterations can be interrogated within the intact joint by combining synchrotron radiation-based microCT with digital volume correlation (DVC) to resolve the loaded osteochondral unit and quantify deformation at the lacuna scale. This highlights the role of articular calcified cartilage in OA-induced load transfer and microdamage. Crucially, translating these high-dimensional tomographic datasets into reliable biomarkers of disease trajectory relies on adopting reproducible, automated quantitative image analysis tools and standardised reporting conventions. Ultimately, advanced tomographic techniques reposition OA imaging from being an endpoint assay to providing temporal, spatial, and functional markers that highlight mechanistic targets for future investigation.