Abstract:

BACKGROUND: Bone morphogenetic protein 4 (BMP-4) and its receptor play an important role in bone regeneration and repair process, but the mechanism is still unclear.
OBJECTIVE: To understand how the mechanical forces are translated into biological signals that regulate bone regeneration and repair, we investigated the expression of BMP-4 and its receptor using a mouse tibia for distraction osteogenesis.
METHODS: A total of 36 healthy male CD-1 mice of 8 weeks old, which were divided into six groups in the experiment, with 6 ones in each group. All animals received placement of the external fixator and osteotomy on the left tibia. Distraction protocol included 5 days latency, 12 days distraction, and 14 days consolidation. Distraction rate was 0. 2 mm, twice a day. The animals were sacrificed at 5, 9, 13, 17, 24, and 31 days after the operation. The lengthened tibiae were harvested and distraction gaps were analyzed by histology, and the expression of BMP-4 and its receptor and osteocalcin was evaluated by using reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. 　
RESULTS AND CONCLUSION: Histological analysis demonstrated that the healing process of osteotomic gap was similar to fracture repair in the latency. RT-PCR and in situ hybridization analysis showed that expression of BMP-4 and its receptor were higher in distraction compared with in latency. The findings from this study suggested that distraction osteogenesis is a unique form of bone regeneration. The mechanic forces induce expression of local growth factors and receptors (such as BMP-4 and ALK-3) that maintain callus formation and remodelling which fill osteotomic gap gradually enlarged by mechanical forces.