Mechanically induced calcium signaling in chondrocytes in situ

Abstract

Changes in intracellular calcium (Ca(2+)) concentration, also known as Ca(2+) signaling, have been widely studied in articular cartilage chondrocytes to investigate pathways of mechanotransduction. Various physical stimuli can generate an influx of Ca(2+) into the cell, which in turn is thought to trigger a range of metabolic and signaling processes. In contrast to most studies, the approach used in this study allows for continuous real time recording of calcium signals in chondrocytes in their native environment. Therefore, interactions of cells with the extracellular matrix (ECM) are fully accounted for. Calcium signaling was quantified for dynamic loading conditions and at different temperatures. Peak magnitudes of calcium signals were greater and of shorter duration at 37°C than at 21°C. Furthermore, Ca(2+) signals were involved in a greater percentage of cells in the dynamic compared to the relaxation phases of loading. In contrast to the time-delayed signaling observed in isolated chondrocytes seeded in agarose gel, Ca(2+) signaling in situ is virtually instantaneous in response to dynamic loading. These differences between in situ and in vitro cell signaling responses might provide crucial insight into the role of the ECM in providing pathways of mechanotransduction in the intact cartilage that are absent in isolated cells seeded in gel constructs.