Received January 4, 2008
Revised January 29, 2008
Accepted after revision February 25, 2008

¹ Sun Yat-sen University
² University of Michigan

^* To whom correspondence should be addressed. E-mail: weizhenz{at}umich.edu.

	Abstract

Our laboratory has 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 defect in rats. Rats with a 9 mm full thickness calvarial bone defect received either Bio-Oss (control group) or Bio-Oss mixed with 20 µg ghrelin (treatment group), followed by local administration of saline or ghrelin (10 µg) on day 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 fluorescent intensity of tetracycline relative to control group. At 6 weeks, bone mineral density increased from 54±7 (control group) to 78±9 mg/cm2 in the treatment group, while the tetracycline fluorescent intensity increased 61±15%. Similar increment was observed at 12 weeks. Quantitative RT-PCR showed that expression of alkaline phosphatase (ALP), osteocalcin, and collagen type I was elevated. Relative to the control, mRNAs for ALP, osteocalcin and collagen type I increased 2.4±0.4 fold, 4.7±1.9 fold 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 the control 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 is a stimulator for intramembranous osteogenesis.

Key Words: Endocrinology, Hormones, Rat