The transmission of physiologic (mechanical) loads requires participation of multiple components of a joint, including bone, muscles, tendons/ligaments and cartilage. Because the function of cartilage is to support time-dependent loading, the response of the tissue and its constituents are extremely important. Not only does cartilage compression causes matrix deformation, but it also deforms the cells within the tissue (Video 1.; Figure 1 & 2). The mechanical deformation of cells within the tissue stimulates cellular metabolism [1, 2] which in turn, regulates the tissue’s environment.
It is this conversion of mechanical signals (from compression) to chemical signals (see ) within the cell that modulate biochemical activity (e.g. protein synthesis see [4-6]) and changes in chondrocyte gene expression (see ) and is referred to as mechanotransduction. Cell-matrix interactions are essential for maintaining the integrity of AC and an intact matrix is essential for the transmission of mechanical signals and hence, cell survival. Because abnormal loading or mechanical injuries to AC are known to shift the balance in catabolic activity over anabolic processes in chondrocytes [1, 2], these can produce degradative processes that may eventually lead to the development of OA.
Research in the field of chondrocyte biomechanics involves understanding how these cells respond to loading, through mechanical deformation. Manipulation of cartilage enzymatically, chemically or through the utilization of surgical interventions (in whole joints) is being performed in order to study how cells respond to mechanical deformation. This research is important in characterizing the tissue’s macro-level tissue properties and/or whole joint-level responses during load bearing.
Video 1: x20-magnification movie of cells being compressed in tissue from bovine patellae cartilage. Cells are stained to fluorescently react to indicate live (green) and dead (red) cells (axis scales are in µm).
Figure 1. x10-magnification image of undeformed cells from bovine patellae cartilage (far left is the surface; far right is bone). Cells in the tissue are stained to fluorescently react to indicate live (green) and dead (red) cells (axis scales are in µm).
Figure 2. x40 magnification 3-D images of cell within the upper zones of bovine patellar cartilage. a) undeformed; b) deformed (at 15% tissue strain). Cells are stained to fluorescently react to indicate live (green) and dead (red) cells (axis scales are in µm).
As mentioned earlier, the damage to the extracellular matrix of cartilage may alter enzymatic pathways of the chondrocyte. Yet, direct observations of these changes are very difficult if not impossible to obtain. However, it is possible to address the effect of mechanical signals between cell-matrix structures with the help of biomechanical modeling. For instance, the aforementioned macro scale loading conditions can be used as input parameters for cell scale biomechanical model.
It is known that the properties of cartilage have a great influence on cell deformations in mechanically loaded cartilage [8-11]. However, limited information exists about the role of different components (collagen, proteoglycans, fluid) in cartilage, and in close proximity to chondrocytes, how these can modulate cell deformation within the tissue.
By implementing experimentally detected cartilage composition data and combining it with experimental loading conditions, we can estimate the effect of these factors in our biomechanical model. Thus, we may address mechanisms for the changes in cell morphology and cartilage at different stages of osteoarthritis. Ultimately, biomechanical models may allow us to find a way to prevent these undesirable changes in the cell morphology, enabling us to restore the cell and tissue functionality.