Cytokines modulate contraction of periosteal explants from rabbit calvariae

Periosteal explants obtained from rabbit calvariae are introduced as a model system to study contraction of soft connective tissue. Culturing of these explants resulted in a substantial time-dependent decrease of the surface area which coincided with a similar decrease in volume. A 75% reduction of the initial explant surface area was observed after a culture period of 72h in the presence of 10% serum. Also in the absence of serum contraction of explants was found, indicating that serum components were not essential. Following devitalization of the explants no contraction did occur. A strong inhibition of contraction was found following interference with the formation of microfilaments, microtubules or intracellular cyclic-AMP levels by using cytochalasin B, colchicine or dibutyryl-cAMP, respectively. These data indicated that viable cells and an intact cytoskeleton were a prerequisite for contraction to occur. A number of cytokines (EGF, aFGF, bFGF, IGF-1, PDGF, TGF-beta and IL-1alpha) was tested for their ability to influence contraction. IL-1alpha was shown to inhibit contraction from the 48h culture period on. Anti-IL-1alpha-serum completely abolished this effect. The IL-1alpha-inducible inhibition of contraction was also partially blocked by indomethacin. TGF-beta enhanced contraction dose-dependently during the 24-48h culture period, whereas TGF-1 and IL-1alpha, added to the cultures in combination, proved to antagonize each other. The other growth factors did neither influence contraction not the IL-1alpha-induced inhibition of contraction.