Local administration of low doses of exogenous BMP2 and leptin promotes ectopic bone regeneration in leptin-deficient mice

BACKGROUND: Obesity and leptin deficiency are associated with compromised bone regeneration. OBJECTIVE: This study aims to investigate the role of locally administrated low-dose BMP2+leptin on bone regeneration in leptin-deficient obese (ob/ob) mice. METHODS: Wildtype (WT) and ob/ob mice were divided into 3 groups (4 mice/group): BMP2 (5 mu g) group, BMP2+low-dose leptin (1 mu g) group, and BMP2+high-dose leptin (2.5 mu g) group. WT mice were used as control mice. An equal size absorbable collagen sponge was prepared by loading the BMP2 or/and leptin and implanted subcutaneously. After 19 days, samples were collected and analyzed by micro- CT and H&E staining. RESULTS: No significant difference in bone regeneration among the three groups in WT mice. Quantification of newly formed bone parameters from micro- CT and H&E staining showed that low-dose BMP2 treatment formed less new bone in ob/ob mice compared to WT. BMP2+low-dose leptin treatment substantially rescued the compromised bone regeneration in ob/ob mice up to the level in WT mice. However, the BMP2 and high dose of leptin failed to rescue the compromised bone regeneration in ob/ob mice. CONCLUSION: Our findings suggest that a combination of the low-dose BMP2 and leptin could be a strategy to promote osteogenesis in obese populations with leptin deficiency.