Leukemia inhibitory factor enhances bone formation in calvarial bone defect

For bone defect reconstruction, locally administered cytokine plasmid was e xamined. Leukemia inhibitory factor (LIF) can bind to the osteoblast cell s urface and induce bone formation both in vitro and in vivo. The authors inv estigated the local mouse LIF complementary deoxyribonucleic acid (cDNA) pl asmid in the pcDNA 3 expression vector, which is promoted by cytomegaloviru s and is stabilized by bovine growth hormone polyadenylation, with a gelati n sponge carrier. A total of 150 male Wistar rats were used. They were divi ded into three groups. Group 1 (N = 30) was treated with the gelatin carrie r of the pcDNA 3 vector, group 2 (N = 90) was treated with three different Roses of LIF cDNA (0.1, 1, and 10 mug) in the pcDNA 3-vector plasmid along with the gelatin carrier, and group 3 (N = 30) was treated with recombinant human bone morphogenetic protein -2. Ten animals in each group were euthan ized at 1, 3, and 5 weeks postoperatively. Animals treated with LIF cDNA sh owed significantly enhanced bone mineral density (p < 0.05), as confirmed b y dual-energy X-ray absorptiometry (DEXA), in 3 weeks compared with the con trol vehicle. By 3 weeks, the number of fibroblastlike cells and collagen f ibers decreased, whereas the osteoblast-like cells increased inversely, as revealed during histological examination. LIF messenger ribonucleic acid de monstrated by in situ hybridization was observed most markedly in osteocyte s of the LIF cDNA-treated group. Also, LIF peptide was detected in the same cell type by immunohistochemistry. Locally administered LIF cDNA plasmid i n a gelatin carrier can increase bone density significantly, with subsequen t bone formation, probably via osteocyte activation.