Stimulation of intramembranous bone repair in rats by ghrelin.

Researchers in our laboratory have previously shown that ghrelin, a gastric peptide hormone, may regulate mesenchymal cell differentiation into adipocytes and myocytes. Here we show that ghrelin promotes osteogenesis of intramembranous bone and improves the repair of calvarial bone defects in rats. Rats with a 9 mm full-thickness calvarial bone defect received either Bio-Oss (control group) or Bio-Oss mixed with 20 mug ghrelin (treatment group), followed by local administration of saline or ghrelin (10 microg), respectively, on days 5, 10 and 15. After 6 and 12 weeks, new bone formation was assessed. Animals treated with ghrelin showed a significant increase in new bone formation as demonstrated by an increment in bone mineral density and fluorescence labelling of tetracycline relative to the control group. At 6 weeks, bone mineral density increased from 54 +/- 7 (control group) to 78 +/- 9 mg cm(-2) in the treatment group, while the tetracycline fluorescence labelling increased by 61 +/- 15%. A similar increment was observed at 12 weeks. Quantitative reverse transcriptase-polymerase chain reaction showed that expression of alkaline phosphatase (ALP), osteocalcin and collagen type I was elevated. Relative to the control animals, mRNAs for ALP, osteocalcin and collagen type I increased 2.4 +/- 0.4-, 4.7 +/- 1.9- and 4.0 +/- 1.7-fold, respectively, in animals treated with ghrelin for 6 weeks (P < 0.05). At 12 weeks, mRNA levels of ALP, osteocalcin and collagen type I showed a decline relative to levels at 6 weeks but still remained significantly higher than in the control group, with fold changes of 2.4 +/- 0.8, 2.4 +/- 1.2 and 2.1 +/- 0.7, respectively (P < 0.05). This study demonstrated that ghrelin stimulates intramembranous osteogenesis.