EXPRESSION AND SPLICING OF THE FIBRONECTIN GENE IN HEALTHY AND DISEASED PERIODONTAL TISSUE

Fibronectin is a major component of the extracellular matrix and is co nsidered to have an important role in chronic inflammatory periodontal disease. The fibronectin gene product has been shown to be subject to alternative splicing in 3 regions, each generating different mRNA tra nscripts associated specifically with normal adult tissue, embryogenes is, tissue regeneration, and wound healing. In the present study, usin g the reverse-transcribed polymerase chain reaction to examine splicin g profiles of the primary transcript, we found that healthy periodonta l tissue expressed all alternatively spliced embryonic isoforms, indic ative of the extensive and ongoing rebuilding processes which occur in these tissues. In marked contrast, only the exon-skipped transcripts were generated in tissue from chronic inflammatory periodontal disease patients. The loss of the high molecular weight isoforms in lesional tissues may be due to the excess production of inflammatory mediators in this disease, since we observed that high concentrations of the cyt okine IL-1 beta caused downregulation of these transcripts in normal p eriodontal cells in tissue culture. Moreover, we also demonstrated tha t growth factors likely to be involved in periodontal regeneration and repair, such as PDGF, IGF-1 and TGF-beta, elicited pronounced upregul ation of the embryonic isoforms of fibronectin in these cells. Althoug h the functional activities of the antigens corresponding to the alter natively spliced variants of fibronectin are not yet known, our findin g that they are selectively expressed suggests that they have highly s pecific rales in both periodontal breakdown and repair.