Determination of the Depth- and Time- Dependent MechanicalBehavior of Mouse Articular Cartilage Using Cyclic Reference PointIndentation

摘要

Mouse models of osteoarthritis and cartilage degeneration are importantand powerful tools for investigating the molecular mechanisms of thedisease pathology. Because of the vast number of genetically modifiedmouse models that are available for research, the ability to use thesemodels is particularly attractive for the mechanobiologic interactionsin the pathogenesis of osteoarthritis. However, the very small scaleof mouse articular cartilage, where the healthy tissue is only 80 µmin thickness, poses challenges in quantifying mechanicalcharacteristics of the tissue. We introduce here a novel approach thatcombines experimental and analytical methods to quantify the nuancedmechanical changes during cartilage degeneration at this scale. Cyclicreference point indentation is used to directly test the murinearticular cartilage to obtain the force-deformation and thephase-shift characteristics of the tissue. The cartilage zonalthicknesses are confirmed from histology. These data are then fittedto a parallel spring model to determine the depth-dependent tissuestiffness and modulus. Using this approach, we investigated theeffects of trypsin degradation on the zonal mechanical behavior ofmouse articular cartilage. We observe a decline of the superficialzone stiffness coupled with the loss of the superficial layer.Subsequent degradation by trypsin allowed the identification ofmiddle- and deep- zone properties. Taken together, this approach canbe a useful tool for understanding the disease mechanisms of cartilagehomeostasis and degeneration, and for monitoring of therapies forosteoarthritis.