The pericellular matrix stiffness is strongly associated with its biochemical and structural changes during the aging and osteoarthritis progress of articular cartilage.However,how substrate stiffness modulates the chondrocyte regulatory volume decrease(RVD)and calcium signaling in chondrocytes remains unknown.This study aims to investigate the effects of substrate stiffness on the chondrocyte RVD and calcium signaling by recapitulating the physiologically relevant substrate stiffness.Our results showed that substrate stiffness induces completely different dynamical deformations between the cell swelling and recovering progresses.Chondrocytes swell faster on the soft substrate but recovers slower than the stiff substrate during the RVD response induced by the hypo-osmotic challenge.We found that stiff substrate enhances the cytosolic Ca2+oscillation of chondrocytes in the iso-osmotic medium.Furthermore,chondrocytes exhibit a distinctive cytosolic Ca2+oscillation during the RVD response.Soft substrate significantly improves the Ca2+oscillation in the cell swelling process whereas stiff substrate enhances the cytosolic Ca2+oscillation in the cell recovering process.Our work also suggests that the TRPV4 channel is involved in the chondrocyte sensing substrate stiffness by mediating Ca2+signaling in a stiffness-dependent manner.This helps to understand a previously unidentified relationship between substrate stiffness and RVD response under the hypo-osmotic challenge.A better understanding of substrate stiffness regulating chondrocyte volume and calcium signaling will aid the development of novel cell-instructive biomaterial to restore cellular functions.

Min Zhang;Xiaoan Wu;Genlai Du;Weiyi Chen;Quanyou Zhang

College of Biomedical Engineering,Taiyuan University of Technology,Taiyuan 030024,China;Department of Physiology and Biophysics,Miller School of Medicine,University of Miami,Miami,FL 33136,USA;Department of Cell Biology and Medical Genetics,School of Basic Medical Science,Shanxi Medical University,Taiyuan 030001,China;Department of Orthopaedics,the Second Hospital of Shanxi Medical University,Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair,Shanxi Medical University,Taiyuan 030001,China

生物化学与生物物理学报（英文版）

[1]Min Zhang;Xiaoan Wu;Genlai Du;Weiyi Chen;Quanyou Zhang-.Substrate stiffness-dependent regulatory volume decrease and calcium signaling in chondrocytes)[J].生物化学与生物物理学报（英文版）,2022(01):113-125

pericellular,Chondrocytes,Ca2+oscillation,Ca2+signaling

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