In Situ measurement of transport between subchondral bone and articular cartilage

摘要

Subchondral bone and articular cartilage play complementary roles in load bearing of the joints. Although the biomechanical coupling between subchondral bone and articular cartilage is well established, it remains unclear whether direct biochemical communication exists between them. The calcified cartilage between these two compartments was generally believed to be impermeable to transport of solutes and gases, previously. However, recent studies found that small molecules could penetrate into the calcified cartilage from the subchondral bone. To quantify the real-time solute transport across the calcified cartilage, we developed a novel imaging method based on fluorescence loss induced by photobleaching (FLIP). Diffusivity of sodium fluorescein (376 Da) was quantified to be 0.07±0.03 and 0.26±0.22 μm²/sec between subchondral bone and calcified cartilage and within the calcified cartilage in the murine distal femur, respectively. Electron microscopy revealed that calcified cartilage matrix contained non-mineralized regions (∼22% volume fraction) that are either large patches (53±18 nm) among the mineral deposits or numerous small regions (4.5±0.8 nm) within the mineral deposits, which may serve as transport pathways. These results suggest that there exists a possible direct signaling between subchondral bone and articular cartilage, and they form a functional unit with both mechanical and biochemical interactions, which may play a role in the maintenance and degeneration of the joint.