The Endogenous Growth Hormone Secretagogue (Ghrelin) Is Synthesized and Secreted by Chondrocytes

Abstract

Ghrelin, the endogenous ligand for the GH secretagogue receptor (GHS-R), is a recently isolated hormone, prevalently expressed in stomach but also in other tissues such as hypothalamus and placenta. This novel acylated peptide acts at a central level to stimulate GH secretion and, notably, to regulate food intake. However, the existence of further, as yet unknown, effects or presence of ghrelin in peripheral tissues cannot be ruled out. In this report, we provide clear evidence for the expression of ghrelin peptide and mRNA in human, mouse, and rat chondrocytes. Immunoreactive ghrelin was identified by immunohistochemistry in rat cartilage, being localized prevalently in proliferative and maturative zone of the epiphyseal growth plate, and in mouse and human chondrocytic cell lines. Moreover, ghrelin mRNA was detected by RT-PCR and confirmed by Southern analysis in rat cartilage as well as in mouse and human chondrocytes cell lines. Ghrelin mRNA expression has been studied in rat along early life development showing a stable profile of expression throughout. Although ghrelin expression in chondrocytes suggests the presence of an unexpected autocrine/paracrine pathway, we failed to identify the functional GH secretagogue receptor type 1A by RT-PCR. On the other hand, binding analysis with 125I ghrelin suggests the presence of specific receptors different from the 1A isotype. Scatchard analysis revealed the presence of two receptors with respectively high and low affinity. Finally, ghrelin, in vitro, was able to significantly stimulate cAMP production and inhibits chondrocytes metabolic activity both in human and murine chondrocytes. In addition, ghrelin is able to actively decrease both spontaneous or insulin-induced long chain fatty acid uptake in human and mouse chondrocytes. This study is the first to provide evidence for the presence of this novel peptide in chondrocytes and suggests novel potential roles for this newly recognized component of the GH axis in cartilage metabolism.

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

“…Likewise, GOAT was also expressed in human immortalized chondrocyte cell lines and in human cultured primary chondrocytes, demonstrating that chondrocytes were equipped with biochemical machinery for the synthesis of acylated ghrelin ). Moreover, ghrelin was synthesized and secreted by chondrocytes (Caminos et al, 2005). These data suggest a novel role of the ghrelin axis in prehypertrophic and hypertrophic chondrocyte differentiation during endochondral ossification.…”

Response of plasma CNP forms to acute anabolic and catabolic interventions in growing lambs

“…It is possible that other nutrition-related hormones released from the gut before or during feeding, such as ghrelin and gastric inhibitory polypeptide (GIP), may be involved in the CNP reduction we observed during caloric restriction. Ghrelin, which is increased in sheep by the anticipation of food (36), inhibits chondrocyte metabolic activity in vitro (6) and is likely to be increased in the caloric-restricted lambs. Also, plasma concentrations of GIP in lambs are known to increase after milk intake (23) and therefore are likely to be low during caloric restriction.…”

GOAT: the master switch for the ghrelin system?

“…In addition to the multiplicity of ghrelin actions affecting GH secretion, food intake, glucose homeostasis, cardiovascular, gastrointestinal and immune functions, it has been reported that ghrelin also plays an important role in bone formation (62) and regulation of chondrocyte metabolism in cartilage (63). Therefore, the expression of GOAT mRNA was also assessed in murine and human chondrocytes.…”