Ghrelin, another factor affecting bone metabolism.

Ghrelin is a 28 amino acid peptide, identified in the stomach of rats and humans, in 1999. It is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R) that strongly stimulates release of growth hormone at the hypothalamus-pituitary axis. In humans, ghrelin exerts a variety of different endocrine and paracrine actions; from increasing food intake (orexigenic effect) to modulating energy homeostasis. It has been proved that ghrelin affects bone metabolism acting by an autocrine/paracrine mode, independent of GH/IGF-1 axis. Recently, ghrelin was identified in osteoblasts, stimulating proliferation and inhibiting apoptosis. Its expression also was confirmed in rat and human cartilage, being prevalently localized in the proliferative and maturative zone of the epiphyseal growth plate (which further supports the hypothesis of ghrelin's action as a growth factor for chondrocytes). Ghrelin also inhibits prostaglandin and/or leukotriene synthesis. Lately, ghrelin promotes osteogenesis of intramembranous bone and improves the repair of calvarial bone defect in rats in vivo. This review summarizes the effects of ghrelin on bone and cartilage metabolism, analyzes its direct and indirect actions on bone cells, and presents the clinical implication for its use.