CARTILAGE FIBRONECTIN ISOFORMS - IN SEARCH OF FUNCTIONS FOR A SPECIALPOPULATION OF MATRIX GLYCOPROTEINS

Fibronectins are a part of the repertoire of matrix molecules produced by the chondrocyte in order to assemble a functional cartilage matrix . They are encoded by a single gene, but significant protein heterogen eity results from alternative RNA splicing. The population of fibronec tin isoforms in adult cartilage is significantly different from fibron ectins in other tissues and includes relatively high levels (20-30 %) of ED-B(+) fibronectins and high levels (50-80 %) of the cartilage spe cific (V+C)(-) isoform which lacks the V, III-15 and I-10 segments. Le ss than 4 % of the fibronectins in cartilage are ED-A(+). The synthesi s and accumulation of cartilage fibronectins are modulated in response to matrix pathology and to biochemical and mechanical mediators. In a ddition, alternative splicing patterns are altered when chondrocytes a re allowed to dedifferentiate in monolayer culture such that the (V+C) (-) isoform is lost but the ED-A(+) isoform is reexpressed at high lev els. Cartilage fibronectins have the potential to participate in cell signalling via integrin mediated pathways and to interact with other c artilage matrix macromolecules. The tissue-specific splicing pattern g ives rise to a unique population of fibronectins within the cartilage. Together, this points to a critical role for cartilage fibronectins i n chondrocyte cell biology and the organization of a biomechanically s ound matrix. However, the precise function (or functions) of the carti lage fibronectins has (or have) not been defined. This minireview exam ines current information about the structure, synthesis and interactio ns of cartilage fibronectins. When possible, potential consequences of the inclusion of the ED-B segment or the exclusion of the V, III-15 a nd I-10 segments are discussed. The goal is to stimulate critical thou ght and discussion in the field about cartilage fibronectin isoforms, their function(s) in normal cartilage, and their role(s) in the pathog enesis of cartilage diseases.