APERTS-SYNDROME - DIFFERENTIAL IN-VITRO PRODUCTION OF MATRIX MACROMOLECULES AND ITS REGULATION BY INTERLEUKINS

During embryonic development, variations in the composition of the ext racellular matrix (ECM) macromolecules influence bone tissue different iation. We present novel findings on the in vitro phenotypic expressio n of periosteal fibroblasts obtained from patients affected by Apert's syndrome, a rare craniofacial malformation, and the effects that inte rleukins (ILs) induce on the phenotype. Apert fibroblasts synthesized greater quantities of glycosaminoglycans (GAGs) and intracellular type I collagen, and also produced more type III collagen and fibronectin. The amount of hyaluronic acid (HA) secreted by Apert fibroblasts was much higher than that secreted by normal fibroblasts, but, as the abso lute values of heparan sulphate (HS), chondroitin sulphate (CS) and de rmatan sulphate (DS) also rose in Apert media, the HA-sulphated GAG ra tio was similar in the media obtained from both populations. Both ns t riggered elevations of HA in normal cells, although relative percentag e secretion remained unaltered, but significantly reduced HA secretion by Apert cells. IL-1 significantly increased CS in normal and Apert m edia, whereas IL-6 enhanced HS and DS in media of both populations. HA -sulphated GAG ratio decreased in Apert media after IL treatment. Both ILs boosted fibronectin production by Apert fibroblasts, whereas IL-1 increased type III but not type I collagen. Taken together, these dat a demonstrate that the synthesis and secretion of ECM macromolecules a re markedly altered in Apert fibroblasts. The fact that treatment with ILs further modifies the Apert phenotype suggests that ILs may be imp licated in the pathophysiology of the malformations during skull morph ogenesis.