title: Accelerated wound closure in vitro by fibroblasts from a subgroup of cleft lip/palate patients: role of transforming growth factor-α.
abstract: In a fraction of patients surgically treated for cleft lip/palate, excessive scarring disturbs maxillary growth and dento-alveolar development. Since certain genes are involved in craniofacial morphogenesis as well as tissue repair, a primary defect causing cleft lip/palate could lead to altered wound healing. We performed in vitro wound healing assays with primary lip fibroblasts from 16 cleft lip/palate patients. Nine foreskin fibroblast strains were included for comparison. Cells were grown to confluency and scratch wounds were applied; wound closure was monitored morphometrically over time. Wound closure rate showed highly significant differences between fibroblast strains. Statistically, fibroblast strains from the 25 individuals could be divided into three migratory groups, namely "fast", "intermediate", and "slow". Most cleft lip/palate fibroblasts were distributed between the "fast" (5 strains) and the "intermediate" group (10 strains). These phenotypes were stable over different cell passages from the same individual. Expression of genes involved in cleft lip/palate and wound repair was determined by quantitative PCR. Transforming growth factor-α mRNA was significantly up-regulated in the "fast" group. 5 ng/ml transforming growth factor-α added to the culture medium increased the wound closure rate of cleft lip/palate strains from the "intermediate" migratory group to the level of the "fast", but had no effect on the latter group. Conversely, antibody to transforming growth factor-α or a specific inhibitor of its receptor most effectively reduced the wound closure rate of "fast" cleft lip/palate strains. Thus, fibroblasts from a distinct subgroup of cleft lip/palate patients exhibit an increased migration rate into wounds in vitro, which is linked to higher transforming growth factor-α expression and attenuated by interfering with its signaling.
authors.affiliation: Department of Orthodontics and Dentofacial Orthopedics, School of Dental Medicine, University of Bern, Bern, Switzerland.
authors.forename: Joël
authors.initials: J
authors.lastname: Beyeler
authors.affiliation: University Clinic for Childrens' Surgery, Bern University Hospital, Bern, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schnyder
authors.affiliation: Department of Orthodontics and Dentofacial Orthopedics, School of Dental Medicine, University of Bern, Bern, Switzerland.
authors.forename: Christos
authors.initials: C
authors.lastname: Katsaros
authors.affiliation: Department of Orthodontics and Dentofacial Orthopedics, School of Dental Medicine, University of Bern, Bern, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Chiquet
mesh_terms: D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002675:Child, Preschool; D002971:Cleft Lip / Q000473:pathology*; D002972:Cleft Palate / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology*; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007223:Infant; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D057134:Antibodies, Neutralizing; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D016211:Transforming Growth Factor alpha; C411423:platelet-derived growth factor C; D066246:ErbB Receptors; D020797:Receptor, Platelet-Derived Growth Factor beta