The internal mechanical functioning of intervertebral discs and articular cartilage, and its relevance to matrix biology
From: Matrix Biol. 2009 Jul 5. [Epub ahead of print]
Degeneration of intervertebral discs and articular cartilage can cause pain and disability. Risk factors include genetic inheritance and age, but mechanical loading also is important. Its influence has been investigated using miniature pressure transducers to measure the distribution of compressive stress (force per unit area) within loaded tissue. The technique quantifies stress concentrations, and detects regions that behave in a fluid-like manner.
Intervertebral discs demonstrate a central fluid-like region which normally extends beyond the anatomical nucleus pulposus so that the whole disc functions like a “water bed”. With increasing age, the fluid region shrinks and pressure within it falls. Stress concentrations appear in the surrounding anulus fibrosus, with location depending on posture. Stress concentrations become large in degenerated discs, and are intensified by sustained loading or injury. Articular cartilage never exhibits an internal fluid pressure: stress gradients and concentrations normally occur within it, and are intensified by sustained loading.
Excessive matrix stresses can cause pain and progressive damage. They also inhibit matrix synthesis and stimulate production of matrix degrading enzymes. In this way, injury to chondroid tissues can initiate a ‘vicious circle’ of abnormal matrix stresses, abnormal metabolism, weakened matrix, and further injury, which explains many features of their degeneration.
Intervertebral discs and articular cartilage facilitate movement and load-transfer in joints. In both of these chondroid tissues, a sparse population of cells maintains an extensive matrix of proteoglycans and collagen, and although the tissues are mostly devoid of blood vessels and nerves, both give rise to pain and disability when affected by degenerative changes. Matrix biology research involving both types of cartilage show some striking parallels, and considerable overlap. There is increasing
recognition that, in both tissues, matrix function and failure depend on complex interactions between genetic inheritance, cell biology, and the mechanical environment.
The intensity of mechanical loading acting within chondroid tissues can be described in terms of stresses and pressures. Stress is the force per unit area acting in or on a solid, and usually varies with location and direction. Pressure is the force per unit area acting in a fluid, and is normally the same in different directions and locations because static fluids have negligible rigidity, and simply deform (flow) to equalise pressure within them. It has been known for many years that the nucleus pulposus of healthy intervertebral discs has such a high water content that it behaves like a fluid, and exhibits a hydrostatic pressure, even though it is sometimes capable of sustaining stress gradients. In contrast, the disc’s anulus fibrosus, and articular cartilage, are fibrous solids with considerable rigidity.
Internal pressures and stresses in chondroid tissues are important for two reasons. High stress concentrations and stress gradients have the potential to disrupt the internal tissue architecture, leading to progressive structural failure as seen in advanced disc degeneration and osteoarthritis (OA). Secondly, cell metabolism is sensitive to stresses and pressure in the surrounding matrix. For example, rounded chondrocytes in articular cartilage and nucleus pulposus increase matrix synthesis in response to moderate hydrostatic pressure, but decrease their synthesis and produce more proteases if the stresses become too high or low. Fibroblast-like cells of the outer anulus respond to cyclic stretching but not to hydrostatic pressure. If cells are dispersed in a soft artificial matrix prior to loading, then realistic cell deformations can be achieved at stress levels less than 1% of those experienced in a living tissue, and yet it is unclear which mechanical signals affect the cells most: stress, or strain (which is % deformation). It is apparent therefore that mechanically-driven failure of chondroid tissues, and cell-mediated responses to mechanical loading, both depend on the nature and distribution of stresses in the extracellular matrix.
Although great efforts are being made to understand how cells respond to their mechanical environment, much less attention has been given to characterising the environment that the cells are responding to. This is unfortunate, because the application of the wrong type or magnitude of loading will lead to very different cell responses, and potentially misleading results.
The internal mechanical environment of chondroid tissues can be studied conveniently using finite element (FE) models. These were first developed to characterise stresses and strains in engineering structures made of simple elastic materials but with complex architecture. Unfortunately, intervertebral discs and articular cartilage have simple structure, but are made from complex fibrereinforced materials which require the models to make many simplifying assumptions. Consequently, FE models of such structures must be validated against experimental measurements before their predictions can be trusted. Experiments are also required to answer fundamental questions such as “how does fluid expulsion under load influence the ability of chondroid tissues to distribute stress evenly on the subchondral bone?” and “how does tissue injury influence stress distributions?”
