Bone Abstracts

Objectives: Ghrelin is a peptide hormone secreted in the stomach, which stimulates GH release and food intake. It is also known to have an effect on bone metabolism. The ghrelin specific receptor, GHS-R1a, belongs to the G protein-coupled receptors (GPCRs). Its downstream pathway in osteoblasts remains unclear. We attempted to clarify the way by which ghrelin acts on osteoblast differentiation.

Methods: We studied two human osteosarcoma cell lines, MG63 and SaOs, previously described as preosteoblastic and osteoblastic cell lines, respectively, which were submitted to ghrelin during differentiation.

Results: Ghrelin stimulated alkaline phosphatase activity, mineralization and expression of RUNX2 in differentiated osteoblastic cells: MG63 previously cultured in osteogenic medium, and SaOs cells. Ghrelin decreased the cAMP content of these differentiated cells. The inhibiting effect of ghrelin on osteoblastic cells cAMP level was reversed by GHRP6 (D-Lys), a GHS-R1a inhibitor. Conversely, in undifferentiated MG63 cells, ghrelin slightly increased proliferation. Lastly, ghrelin increased the expression of GHS-R1a. Overall, our data showed that ghrelin contributes to progression in the osteoblastic lineage of already differentiated osteoblasts only, and not of undifferentiated cells. It is therefore suggested that GHS-R1a along the differentiation of osteoblastic cells contributes to their optimal differentiation.

Conclusion: These results emphasize the potential role of ghrelin and GHS-R1a in the regulation of bone formation and maturation of osteoblasts. They may have consequences in pathophysiological conditions like puberty or anorexia, both known to significantly modify ghrelin secretion.