Expression of Smads in Distraction Osteogenesis of Rat Mandibles

Abstract

The transforming growth factor-beta (TGF-beta) super family includes TGF-beta and bone morphogenetic proteins (BMP) which play an important role during fracture healing and distraction osteogenesis. Smads are intracellular signal transmission mediators of BMP and TGF-beta. Smad 1, 5, 8 are receptor-regulated Smads (R-Smad) which transmits signals of BMPs. Smad 2, 3 are receptor-regulated Smads (R-Smad) which transmits signals of TGF-beta. Smad 4 is a common partner Smad (Co-Smad) which combines signal transmissions of R-Smads. Smad 6, 7 are inhibitory Smads (I-Smad) which inhibits signal transmissions of R-Smads. The aim of this study was to evaluate the expression of R-Smads, Co-Smad, I-Smads, BMP-2, 4 and TGF-beta in distraction osteogenesis of rat mandibles.
Left mandibular osteotomy was performed and fixed with an external distractor in 30 rats. After a latency period of 5 days, the mandible was lengthened at a rate of 0.4 mm/day for 8 days (total 3.2 mm). Animals were sacrificed immediately after latency, during distraction, immediately after completion of distraction and after 7 days and 14 days of consolidation. Immunohistochemical analysis was performed to investigate the expressions of R-Smads, Co-Smad, I-Smads, BMP-2, 4 and TGF-beta. Expression of Smad 1, 2, 3, 5, 8, BMP-2, 4 and TGF-beta increased during the distraction phase and gradually decreased towards the consolidation period. On the other hand, expression of Smad 6, 7 was low during the distraction phase, while it increased during the consolidation period. Smad 1, 5, 8 showed a spatial and temporal pattern of expression similar to that of BMP-2, 4 during distraction osteogenesis. Similarly, Smad 2, 3 showed a similar expression pattern to TGF-beta. The increase in expression of I-Smads after completion of distraction indicates its role in the bone remodeling and maturation process.