The effect of leptin on the osteoinductive activity of recombinant human bone morphogenetic protein-2 in nude mice.

OBJECTIVE: To investigate the effect of leptin in the model of ectopic bone formation that utilizes subcutaneously implanted recombinant human bone morphogenetic protein-2 (rhBMP-2)-containing type I collagen discs. METHODS: This study was performed in the Clinical Research Center, Southern Medical University, Guangzhou, China from November 2008 to June 2009. A single dose of 20 ul saline (group A), 20 ug leptin (group B), 2 ug rhBMP-2 (group C), 2 ug rhBMP-2 + 20 ug leptin (group D), and type I collagen disks as a carrier were mixed, and subcutaneously implanted into the back of nude mice (n=12). The effect of ectopic bone formation was evaluated by radiography, dual-energy X absorptiometry, biochemical examination of alkaline phosphatase (ALP) activity, histological observation, and semi-quantitative evaluation 4 and 8 weeks after surgery. RESULTS: At 4 and 8 weeks after operation the radiographs, bone mass density, ALP, and histology values showed significant intragroup and intergroup differences, with those at 8 weeks being higher than those at 4 weeks. CONCLUSION: Our results indicated that the sustainedly released material with collagen as a carrier combined treatment with leptin and rhBMP-2 has a very good osteoinductive activity. Leptin is a positive modulator for the osteoinductive efficacy of BMPs, they have synergistic effect. Its mechanisms are probably related to promote the formation of new-vessels and proliferation/ differentiation of many kinds of cells.