Ghrelin increases beta-catenin level through protein kinase A activation and regulates OPG expression in rat primary osteoblasts
Articolo
Data di Pubblicazione:
2015
Citazione:
Ghrelin increases beta-catenin level through protein kinase A activation and regulates OPG expression in rat primary osteoblasts / E. Mrak, L. Casati, F. Pagani, A. Rubinacci, G. Zarattini, V. Sibilia. - In: INTERNATIONAL JOURNAL OF ENDOCRINOLOGY. - ISSN 1687-8337. - 2015(2015 Mar), pp. 547473.1-547473.10. [10.1155/2015/547473]
Abstract:
Ghrelin, by binding growth hormone secretagogue receptor (GHS-R), promotes osteoblast proliferation but the signaling mechanism of GHS-R on these cells remains unclear. Since canonical Wnt/β-catenin pathway is critically associated with bone homeostasis, we investigated its involvement in mediating ghrelin effects in osteoblasts and in osteoblast-osteoclast cross talk. Ghrelin (10-10M) significantly increased β-catenin levels in rat osteoblasts (rOB). This stimulatory action on β-catenin involves a specific interaction with GHS-R1a, as it is prevented by the selective GHS-R1a antagonist, D-Lys3-GHRP-6 (10-7M). The effect of ghrelin on β-catenin involves the phosphorylation and inactivation of GSK-3β via protein kinase A (PKA). Inhibition of PKA activity reduces the facilitatory action of ghrelin on β-catenin stabilization. Ghrelin treatment of rOB significantly increases the expression of osteoprotegerin (OPG), which plays an important role in the regulation of osteoclastogenesis, and this effect is blocked by D-Lys3-GHRP-6. Furthermore, ghrelin reduced RANKL/OPG ratio thus contrasting osteoclastogenesis. Accordingly, conditioned media from rOB treated with ghrelin decreased the number of multinucleated TRAcP+ cells as compared with the conditioned media from untreated-control rOB. Our data suggest new roles for ghrelin in modulating bone homeostasis via a specific interaction with GHSR-1a in osteoblasts with subsequent enhancement of both β-catenin levels and OPG expression.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Endocrine and Autonomic Systems; Endocrinology; Endocrinology, Diabetes and Metabolism
Elenco autori:
E. Mrak, L. Casati, F. Pagani, A. Rubinacci, G. Zarattini, V. Sibilia
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