Local Strain Distribution and Increased Intracellular Ca2+ Signaling in Bovine Articular Cartilage Exposed to Compressive Strain

Abstract

Articular cartilage is exposed to compressive strain of approximately 10% under physiological loads in vivo, and intracellular Ca2+ signaling is one of the earliest responses in chondrocytes under this physical stimulation. However, it remains unknown whether compressive strain itself evokes intracellular Ca2+ signaling in chondrocytes located within each layer (from surface to deep) in an equal manner with physiological levels of strain. The purpose of this study, therefore, was to determine the distribution of local strain and increased intracellular Ca2+ signaling in layer-dependent cell populations in response to 10% compressive strain loading. For this purpose, the time course of strain was measured in each layer to calculate layer-specific deformation properties. In addition, layer-specific changes in chondrocyte intracellular Ca2+ signals were recorded over time using a fluorescent Ca2+ indicator, Fluo-3, to establish ratios of cells with increased Ca2+ signaling at each depth of cartilage under static conditions or exposed to compression. The results showed that the surface layer was compressed with a larger strain compared with other layers. Few cells with Ca2+ signaling were observed under static conditions. Percentages of responsive cells within compressed cartilage were higher than those within cartilage under static conditions. However, increased intracellular Ca2+ signals were observed in a prominent number of chondrocytes within the deep layer, but not the surface layer, of compressed cartilage. Our results suggest that at a physiological compression level, Ca2+ is upregulated, but the stimulation of Ca2+ signaling in articular cartilage is not simply defined by local deformation.