The Collagen and the GAG's
Example of Osteo-Arthritis
Tissue Remodelling in Labour
Therapeutic Approaches
Where Next? The cellular components of connective tissue and bone are sensitive to mechanical stimuli, possibly through an electrical transduction of the mechanical signal. The tissue cells must then alter their synthesis of the components which constitute the tissue matrix and which determine its mechanical properties.
In all connective tissues, collagen is the principle mechanical component and exists as a fibre reinforcement. Metabolically, collagen is very stable, remodelling very slowly. Glycosaminoglycans (GAGs) comprise another tissue component which is modified by the cells rapidly and such modifications are sensitive to applied mechanical loads. These GAGs are also able to modify the mechanical behaviour of tissues, which makes them a prime candidate for a biochemical mediator in the above biomechanical control loop.
How can the GAGs be so effective in remodelling the properties of collagenous tissues in which they are a minority component? They must control the interactions and links through which the tissue micro-structure derives its mechanical integrity. In this role the GAGs will determine how the applied mechanical energy is stored and dissipated in the visco-elastic tissues.
Dysfunction of the above biomechanical control loop may be involved in a number of disease processes. Take the degeneration of articular cartilage in osteo-arthritis as an example. The GAGs of articular cartilage are modified by mechanical stimuli and correlate with the visco-elastic behaviour of the tissue. The GAG composition of cartilage also changes with age and disease. Numerous causal factors have been implicated in the development of osteo-arthritis:
All of the above can be seen as perturbing the biomechanical control mechanism. Such a multifactorial aetiology occurs with other connective tissue diseases and the biomechanical control paradigm may be useful to define an appropriate therapeutic rationale. After all, like articular cartilage, the role of all connective tissues is to connect. Their mechanical properties are fundamental to their function.
Musculo-skeletal tissues generally respond to mechanical stress in a fairly sedate manner unless injury is involved. However, there is a more dramatic example of tissue remodelling which demonstrates the speed and power of the process. Throughout pregnancy the cervix fulfills a mechanical function, keeping the contents of the uterus in place. The collagen is organised to support this function, being tightly packed and circumferentially orientated in the cylindrical cervix, making the tissue a stiff visco-elastic solid to resist dilatation. Yet, within 24 hours of parturition, the situation must dramatically change as the sphincter must become a passage for the birth of the foetus:-
The result is a modified cervical and lower uterine tissue in which the collagen is randomly dispersed in a GAG matrix. This tissue is able to sustain strains of 1000% as it is deformed around the ellipsoidal foetal head. In fact, the tissue now behaves as a visco-elastic liquid, able to elongate constantly under the action of an applied force. Such a fundamental change is achieved through the re-organisation of the tissue micro-structure.
Then, a further 24 hours after the birth, a tissue structure and properties are being restored and are close to their original non-pregnant behaviour.
The above biomechanical control loop for connective tissues offers the opportunity for therapeutic intervention at any point in the links of the chain.
A wider perspective of this therapeutic paradigm can be found in 'Catching up the Orthopods' (British Medical Journal 297: 936 1988.)
Much remains to be discovered to enable a constructive intervention in the remodelling processes of connective tissues and bone. However, one thing is clear. To understand the processes in any control loop one must be prepared to take the holistic view. One could never learn how to drive a car by studying the wheel alone!
Mechanical Results Gallery to see how the visco-elastic behaviour of articular cartilage changes with age.