Chondrocyte metabolism is stimulated by mechanical loading and is associated with structural changes in the cartilage extracellular matrix (ECM). Calcium signaling is an initial step in the biological response of cells to mechanical loading. The purpose of this work was to measure local ECM and chondrocyte deformations for a range of tissue strains and to relate the measured deformations to chondrocyte calcium signaling in intact cartilage attached to its native bone. We observed that:​

1. Chondrocytes are protected from excessive deformation when cartilage is subjected to extreme compressive strains, likely due to the local extra- and pericellular matrices;​
2. Chondrocyte calcium signaling is strongly correlated to compressive loading magnitude and the local ECM strains within the tissue;​ and,
3. Chondrocyte mechanobiology varies topographically within a joint.

These results provide new insights into the relationship between compressive mechanical loading, the resulting tissue and cell deformations, and the calcium signaling response of the chondrocytes.