The Expression Of BMP-4/ALK-3 In Distraction Osteogenesis Of Mouse Tibia

Objective:Establish model of mouse tibia for distraction osteogenesis,To understand how the mechanical forces are translated into biological signals that regulate bone regeneration and repair, we investigated the expression of Bone Morphogenetic protein 4(BMP-4) and its receptor activin -like kinase3(ALK-3) using a mouse tibia for distraction osteogenesis.Methods:Thirty - six male CD - 1 mice,8 weeks old, were used in the study. All animals received placement of the external fixators 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/day. The animals were sacrificed at 5,9,13,17,24, and 31days after the operation. The lengthened tibiae were harvested and distraction gaps were analyzed by histology, RT - PCR, and in situ hybridization.Results:Histological analysis demonstrated that the healing process of osteotomic gap was similar to fracture repair in the latency. The distraction callus consisted of fibrous interzone, primary matrix front, and microcolumn formation during the distraction. In the early stage of consolidation the distraction gap was bridged by bony callus. RT - PCR and in situ hybridization analysis showed that mechanical forces enhanced expression of BMP - 4 and ALK-3.Conclusions:1.Our data 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.2.The primary mode of bone formation in the new bone is intramembranous ossification.