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806   Chapter 7


                                                                  Intermittent  pressures  created  by the  interaction  of
            Biomechanics                                       the opposing articular surfaces pump fluid through the
              As indicated previously, articular cartilage is a tissue
  VetBooks.ir  consisting of aggrecan that is stiff in compression, col­  cartilage for nutrition and the removal of metabolic by‐
                                                                        63
                                                               products.  Expressed fluid from the articular cartilage
            lagen that is stiff and strong in tension, and somewhat
                                                               resembles synovial fluid except for its low protein con­
            freely moving fluid carrying mobile ions (interstitial
                                                                               49
            fluid). These components interact to provide the follow­  tent and viscosity.  It has been shown that the concen­
                                                               tration of fixed charges from GAG is the prime
            ing mechanical and physical characteristics when young                              56
            and healthy: (1) a permeable matrix that is stiff in com­  determinant of cartilage permeability.  Simple diffusion
                                                               seems sufficient for nutrition of all but the deepest layers
            pression, (2) a fibrous network capable of withstanding
            high tensile stresses, (3) a fluid that flows under load or   of articular cartilage, but joint movement probably
                                                               facilitates the process.
            deformation and aids in dissipating high stresses in the
                                                                  Studies have shown that proteoglycans restrict solute
            tissue, and (4) a high swelling pressure that results in a   movement within the tissue matrix. The proteoglycans
                                   73
            matrix swollen with water.  It has also been noted that
            an important function of aggrecan in cartilage is to   restrict the diffusion of large, uncharged solutes but do
                                                               not affect the diffusion of small, uncharged solutes. The
            retard the rate of stretch and alignment when a tensile
            load is suddenly applied and that this mechanism may   molecular size and conformation of the solute is also an
                                                               important factor. Removal of proteoglycans increases
            be useful in protecting the cartilage collagen network
            during physiologic situations. 97                  the influx of large molecules into the matrix, and this
                                                               suggests that proteoglycan removal may also increase
              In an unloaded joint, the opposing articular surfaces                                           108
            are not completely congruent.  However, under physio­  the efflux of large molecules out of the tissue matrix.
                                     28
                                                               It has been suggested that the marked loss of aggrecan
            logic loading, because the cartilage is soft, deformation
            causes an increase of contact area (reducing tissue stress   and newly synthesized proteoglycan monomer from the
                                                               matrix in osteoarthritis (OA) is probably a direct result
            levels) and increases joint conformity (which provides
            additional stability).  The adaptation of the shape of   of the increased mobility of these macromolecules as the
                                                               tissue matrix components continue to degrade.
            loaded cartilage may also help to form and retain bound­
                                                                  It is also well accepted that mechanical forces modu­
            ary lubrication (see below). As articular cartilage directly   late the metabolic activity of chondrocytes; clarification
            under load is compressed, the surrounding areas are sub­
            jected to transverse tensile strains. These forces tend to   of the specific mechanisms of mechanical signal trans­
                                                               duction in articular cartilage is emerging.  One pro­
                                                                                                     71
            redistribute fluid away from the compressed area and
            into the stretched regions. As mentioned previously, the   posed pathway is that chondrocytes may perceive
                                                               changes in their mechanical environment through cellu­
            major contribution to the osmotic pressure provided by            33
            the proteoglycans is derived from negatively charged sul­  lar deformation.  More recently it is demonstrated that
                                                               the  chondrocytes  possess  a  primary  cilium  that  is
            fate and carboxyl groups of the GAG and the associated
            cations (ionic or Gibbs–Donnan effect).  Water  is   involved in mechanotransduction events related to carti­
                                                 108
                                                               lage extracellular matrix synthesis.   This study con­
                                                                                               114
            attracted by the high charge density, and this osmotic
            pressure may contribute up to 50% of the compressive   firmed that primary cilia were essential organelles for
                                                               cartilage mechanotransduction, as well as identified a
            stiffness of the articular cartilage. The swelling pressure is
            balanced by the tensile stress of the collagen framework.  novel role for primary cilia not previously reported in
                                                               any other cell type, namely, cilia‐mediated control of
              Mow and colleagues have described the extracellular
            matrix as a cohesive porous composite.  Their biphasic   ATP reception. It is well established that the GAG con­
                                              73
                                                               tent of habitually loaded areas of cartilage is greater
            model for articular cartilage considers the tissue as
            an  interacting  mixture of two continuums:  a porous   than that of habitually unloaded areas. Work in sheep
                                                               stifle joints has shown that different areas of articular
              permeable elastic solid and interstitial fluid. Because of
            swelling pressure, the collagen network of the articular   cartilage subjected to differing mechanical stresses con­
                                                               tain a phenotypically distinct chondrocyte population.
                                                                                                              50
            cartilage is under a tensile prestress even when unloaded.
            During compression, the concentration of the organic   Chondrocyte phenotypes were identified by the relative
                                                               biosynthesis of aggrecan, biglycan, and decorin.
            material and the charge density increase because the
            interstitial fluid is forced to flow from the matrix. A new   Articular Cartilage Metabolism and Matrix Turnover
            equilibrium is reached when the charge density, collagen
            tension, and applied load are in balance (Figure  7.7).   The chondrocytes synthesize all of the components of
            The deformation of this cartilage in association with   the cartilage matrix. At each stage of growth, develop­
            fluid exudation is called creep. The compression time   ment, and maturation, the relative rates of matrix syn­
            curve consists of the creep phase, controlled by fluid   thesis  and degradation are adjusted  to achieve net
            exudation, and the second phase, which is related to   growth, remodeling, or equilibrium. A unique interac­
            the  collagen proteoglycan matrix component. During   tion exists between chondrocytes and the surrounding
            prolonged periods of stationary loading, fluid is slowly   matrix. This may be facilitated by a cilium from each
            exuded and redistributed within the cartilage until an   chondrocyte that extends into the matrix and acts as a
            equilibrium position is reached.  At this stage, the   probe, sensing changes in the matrix composition such
            increased concentration of the fixed charge density is   as a loss of proteoglycan or collagen or an increase or
            counterbalanced by the increased osmotic swelling   decrease in HA concentration.  This information is
              pressure of the proteoglycan.  When fluid motion   relayed to the cell. Interaction between the pericellular
            ceases,  the  entire external load is borne by the solid   and territorial matrix and the chondrocyte cell
            extracellular matrix.                                membrane also may include transmission of mechanical
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