Nanoindentation modulus of murine cartilage: a sensitive indicator of the initiation and progression of post-traumatic osteoarthritis

Abstract

Objective This study aims to demonstrate that cartilage nanoindentation modulus is a highly sensitive indicator of the onset and spatiotemporal progression of post-traumatic osteoarthritis (PTOA) in murine models. Design Destabilization of medial meniscus (DMM) surgery was performed on the right knees of 12-week old male, wild-type C57BL/6 mice, with Sham control on contralateral left knees. Atomic force microscopy (AFM)-based nanoindentation was applied to quantify the nanoindentation modulus, Eind, of femoral condyle cartilage at 3 days to 12 weeks after surgery. The modulus changes were compared against the timeline of histological OA signs. Meanwhile, at 8 weeks after surgery, changes in meniscus, synovium and subchondral bone were evaluated to reveal the spatial progression of PTOA. Results The modulus of medial condyle cartilage was significantly reduced at 1 week after DMM, preceding the histological OA signs, which only become detectable at 4 – 8 weeks after. This reduction is likely due to concomitantly elevated proteolytic activities, as blocking enzymatic activities in mice can attenuate this modulus reduction. In later OA, lateral condyle cartilage and medial meniscus also started to be weakened, illustrating the whole-organ nature of PTOA. Conclusions This study underscores the high sensitivity of nanoindentation in examining the initiation, attenuation and progression of PTOA in murine model. Meanwhile, modulus changes highlight concomitant changes in lateral cartilage and meniscus during the advancement of OA.

EGFR signaling is critical for maintaining the superficial layer of articular cartilage and preventing osteoarthritis initiation

“…5B). These data also match our current observation that DMM surgery rapidly reduced surface E ind of WT mouse cartilage (16). Taken together, our results clearly demonstrate that EGFR signaling regulates mechanical properties of articular cartilage.…”

“…7D). As OA further develops, the DMM site of WT mice also exhibited the same or elevated E ind compared with the sham site (16). Fourth, pain is the major symptom in OA.…”

Indentation mapping revealed poroelastic, but not viscoelastic, properties spanning native zonal articular cartilage

“…Yet it is likely that these behaviors vary with the underlying chemistry and extracellular matrix organization in zonal cartilage. Indentation of the articular surface has evaluated equilibrium properties of native, diseased, and repair cartilage [24–28] and begun to explore the time-dependent response [9,22,29,30]. Results were combined with finite element models [21,31] and correlated with chemistry in maps spanning osteochondral tissues [32–34].…”

Functional properties of chondrocytes and articular cartilage using optical imaging to scanning probe microscopy

“…Micro‐sized tips showed no change in stiffness until much later stages of degeneration, at which point compliance decreased. Han et al showed that a decrease in surface stiffness could be observed as early as one week after injury in a small animal model of post‐traumatic osteoarthritis . While most AFM approaches rely on simple elastic indentation tests, Grodzinsky et al used microrheology in conjunction with a poroelastic model to determine parameters like the Young's modulus of the fibrillary and non‐fibrillary components and the hydraulic permeability .…”

“…Han et al showed that a decrease in surface stiffness could be observed as early as one week after injury in a small animal model of post-traumatic osteoarthritis. 67 While most AFM approaches rely on simple elastic indentation tests, Grodzinsky et al used microrheology in conjunction with a poroelastic model to determine parameters like the Young's modulus of the fibrillary and non-fibrillary components and the hydraulic permeability. 68 With this type of approach, increased fluid flow in in the tissue was noted as an early and sensitive microscale marker of cartilage degradation.…”