“…Within their ECM, chondrocytes are surrounded by a narrow (2–4 μm thick) pericellular matrix (PCM) that is both biochemically and biomechanically (Young’s modulus 23–59 kPa) distinct from the ECM (Young’s modulus ≈500 kPa) and together with the ensconced cells is referred to as a chondron ( Mow and Guo, 2002 ; Guilak et al, 2005 ; Gao et al, 2014 ; Chery et al, 2021 ). The extra- and pericellular matrix zones transmit the depth-dependent dynamic mechanical stimuli, comprising a combination of compression, hydrostatic pressure, shear stress, osmotic stress, and tensile strain, to the mechanosensitive chondrocytes, which in turn adjust cartilage metabolism depending on the magnitude, frequency, strain rate and nature of the applied load ( Natenstedt et al, 2015 ; Gilbert et al, 2021 ; Statham et al, 2021 ). The bidirectional reciprocity in cartilage mechano-signaling enables chondrocytes to sense load application, including altered loading patterns, and in turn adjust matrix composition in response to mechanical cues.…”