Mechano-Biology of Chondrocytes in Intact Joints Under Muscular Loading

Abstract

It is well documented that onset and progression of OA is directly related to the mechanical loading of joints, and the associated mechano-biology of chondrocytes. However, work on the mechano-biology of chondrocytes has been performed with isolated cells or tissue explants subjected to confined and unconfined loading, conditions which neglect the role of the matrix and ignores the boundary conditions of cartilage-on-cartilage contact, and fails to reproduce physiological loading conditions.We developed a novel approach which allows quantification of chondrocyte mechanics, signaling and analysis of proteins, cytokines and fluid borne stem cells contained within the synovial fluid of intact knees in live mice while the joint is loaded using controlled muscular stimulation.Chondrocytes and their nuclei deform on average 18-25% for sub-maximal muscular loading in the intact mouse knee. Deformation occurs “instantaneously” upon loading, but requires minutes for full recovery (Figures 1a). High muscular loading of the mouse knee caused an increase in total protein content in the synovial fluid (Figure 1b) and an increase in PRG4 (also known as lubricin). When “high” intensity load conditions were repeated, the PRG4 and total protein release was stopped (Figure 1b).View Large Image | View Hi-Res Image | Download PowerPoint Slide