Articular cartilage is a highly specialized connective tissue wrapped around joint ends, contributing to load bearing and friction reduction. The absence of blood vessels and nerves hinders cartilage self-repair after damage (Buckwalter, 1998, Cai et al., 2021). With accumulating damage, cartilage further degenerates, ultimately progressing into osteoarthritis (OA). Among lower extremity joints, the knee is the most frequently affected site (Oliveria et al., 1995). Currently the fourth leading cause of disability, OA has become a significant public health concern globally (Fransen et al., 2011).

Three main phenotypes that comprise knee OA have been identified: post-traumatic OA, aging-related OA, and metabolic OA (Bijlsma et al., 2011). Excessive/abnormal mechanical load is the main factor for the onset and progression of post-traumatic OA because permanent damage to cartilages can occur under high mechanical loads (Khajehsaeid and Abdollahpour, 2020). The high mechanical loads might stimulate enzymatic activities, promotes proteoglycan degradation, and destroy collagen networks (Kurz et al., 2005, Loeser, 2006). It was found that knee OA is 4.2 times more likely to occur in individuals with traumatic history than in healthy ones (Muthuri et al., 2011). Moreover, large dynamic load (particularly high load impulse) has been concluded to accelerate the progression of knee OA (Bennell et al., 2011, Miyazaki et al., 2022). Doyran et al. (2017) suggested that nanoindentation modulus is a highly sensitive indicator for evaluating the onset and progression of post-traumatic OA in murine models. It was reported that the elastic modulus and hardness of knee joint cartilages under high weight bearing significantly decrease relative to those under low weight bearing (Mieloch et al., 2019, Collins et al., 2021). In aging-related OA, the composition and microstructure of cartilages undergo significant changes, such as increased thickness of the calcified layer, fragmented and heterogeneous proteoglycans, and decreased chondrocyte density and water content (Platt et al., 1998, Gupta and Goyal, 2006, Varela-Eirin et al., 2018). However, the effect of aging on the mechanical properties of cartilage remains inconclusive. The shear modulus of cartilage in the human knee joint is strongly correlated to age (Peters et al., 2018), whereas age exerts no significant effect on the mechanical properties of cartilage for some commonly used experimental rats (Athanasiou et al., 2000, Wang et al., 2006). Furthermore, the alterations of collagen network during the progression of OA were quantitatively characterized and included in joint numerical simulations to investigate the potential influence of collagen fibrils (; Mononen et al., 2011, Mononen et al., 2016; Rasanen et al., 2013).

Metabolic OA is another main phenotype of OA (Bijlsma et al., 2011). Type 2 diabetes mellitus (T2DM), a major metabolic disorder, negatively affects cartilages and joints because of oxidative stress, pro-inflammatory cytokines, chronic high glucose concentration, and insulin resistance (Courties and Sellam, 2016, Veronese et al., 2019, Eitner and Wildemann, 2021). Healthy and diabetic cartilages have been compared with respect to surgeon score, histology staining, immunohistochemistry, quantitative magnetic resonance imaging, and enzyme-linked immunosorbent assay (Onur et al., 2014, Neumann et al., 2018; Wang et al., 2021). These results indicate that T2DM accelerates cartilage matrix degeneration and affects disease onset and progression. However, whether the mechanical properties of diabetic cartilages change remains unknown and needs to be determined. Herein, we quantitatively investigated healthy and diabetic cartilages by scanning electronic microscopy (SEM), X-ray energy spectroscopy, histological staining, and microindentation. We hypothesized that T2DM significantly alters the microstructural, compositional, and mechanical properties of cartilages. The results can elucidate the progression of diabetic OA in T2DM patients and contribute to the development of scientific diagnosis and treatment for the disease.