In situ measurement of transport between subchondral bone and articular cartilage

Abstract

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. Previously, the calcified cartilage between these two compartments was generally believed to be impermeable to transport of solutes and gases. 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 AE 0.03 and 0.26 AE 0.22 mm 2 /s 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 nonmineralized regions ($22% volume fraction) that are either large patches (53 AE 18 nm) among the mineral deposits or numerous small regions (4.5 AE 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. ß

Gap junction permeability between tenocytes within tendon fascicles is suppressed by tensile loading

“…Thus, connexin 43 appears a likely candidate for the predominant gap junction protein involved and is also reported to exhibit mechanosensitive expression in other cell types (DePaola et al 1999;Garcia and Knight 2010). To date, only few theoretical models have been reported to provide further analysis of FLIP data (Pan et al 2009). Accordingly, a 2-dimensional compartment model of the FLIP protocol was developed to derive a parameter relating to intercellular permeability k, independent of specific imaging protocols.…”

Stereologic Analysis of Tibial-Plateau Cartilage and Femoral Cancellous Bone in Guinea Pigs With Spontaneous Osteoarthritis

“…The reduction in the thickness of the calcified cartilage layer could be attributable to a systematic process of demineralization in the activated joint [31], vascular invasion of the subchondral bone [18], or both phenomena. Changes in the mineral content and thickness of the calcified cartilage layer conceivably play a more prominent role in the pathogenesis of OA than has been hitherto supposed [6,30]. The process of demineralization associated with the rapid remodeling of osseous tissue results in a net reduction in bone stiffness and in support for the cartilage layer, which responds with an increase in matrix production [7,34].…”

Subchondral Bone in Osteoarthritis

“…The first is that poor perfusion in the subchondral bone may also result in a decrease in nourishment to the overlying cartilage, as proposed by Imhof et al (1997). More recently, Pan et al (2009) were one of several groups to show that small molecules can penetrate into the calcified cartilage from the subchondral bone. In elegant experiments, they used fluorescence and photobleaching methods to demonstrate that fluorescein can diffuse between subchondral bone and articular cartilage, and that these compartments form a functional unit with biochemical as well as mechanical interactions.…”