The role of transforming growth factor-beta, insulin-like growth factor I,and basic fibroblast growth factor in distraction osteogenesis of the mandible

Distraction osteogenesis is a viable method for regenerating large amounts of bone. In contrast to fracture healing, the mode of bone formation in dis traction osteogenesis is primarily intramembranous ossification. The basic biology of the process is still not well understood. The growth factor casc ade is likely to play an important role in distraction. This study examines the growth factor cascade in a lengthened ovine mandible model. Twenty-fou r animals were divided into four groups with varying rates of distraction ( 1, 2, 3, and 4 mm/day). A unilateral distracter at the angle of the mandibl e was used. The mandibles were lengthened to 24 mm and fixed for a period o f 5 weeks, after which the animals were killed. The sections were probed fo r transforming growth factor-beta, basic fibroblast growth factor, and insu lin-like growth factor I. The growth factors studied were present in all fo ur groups. Transforming growth factor-beta, basic fibroblast growth factor, and insulin-like growth factor I were present in both the bony matrix of t he sections and the cytoplasm of the cells, osteoblasts, and a small number of mesenchymal cells. The sections obtained from groups distracted at fast er rates showed stronger presence of the growth factors examined by more in tense staining. In fracture healing, the localization of transforming growt h factor-beta in stage I of healing corresponded with the precise region of intramembranous ossification in stage II. Diffuse presence of transforming growth factor-beta throughout the lengthened region corresponded with the process of intramembranous ossification observed in distraction. In fractur e healing, insulin-like growth factor I and basic fibroblast growth factor have been shown to promote proliferation and differentiation of osteoblasts from precursor cells. The intense presence of insulin-like growth factor I and basic fibroblast growth factor in the distracted region may account fo r osteoblast proliferation and formation from precursor mesenchymal cells. Mechanical strain has been shown to increase the expression of transforming growth factor-beta and insulin-like growth factor I. Distraction may serve as a source of mechanical strain, which may explain, in part, the expressi on of these growth factors, particularly in the faster groups.