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Ghrelin Increases Beta-Catenin Level through Protein Kinase A Activation and Regulates OPG Expression in Rat Primary Osteoblasts
Joint Authors
Zarattini, Guido
Mrak, Emanuela
Casati, Lavinia
Pagani, Francesca
Rubinacci, Alessandro
Sibilia, Valeria
Source
International Journal of Endocrinology
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-03-17
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Mrak, Emanuela& Casati, Lavinia& Pagani, Francesca& Rubinacci, Alessandro& Zarattini, Guido& Sibilia, Valeria. 2015. Ghrelin Increases Beta-Catenin Level through Protein Kinase A Activation and Regulates OPG Expression in Rat Primary Osteoblasts. International Journal of Endocrinology،Vol. 2015, no. 2015, pp.1-10.
https://search.emarefa.net/detail/BIM-1065743
Modern Language Association (MLA)
Mrak, Emanuela…[et al.]. Ghrelin Increases Beta-Catenin Level through Protein Kinase A Activation and Regulates OPG Expression in Rat Primary Osteoblasts. International Journal of Endocrinology No. 2015 (2015), pp.1-10.
https://search.emarefa.net/detail/BIM-1065743
American Medical Association (AMA)
Mrak, Emanuela& Casati, Lavinia& Pagani, Francesca& Rubinacci, Alessandro& Zarattini, Guido& Sibilia, Valeria. Ghrelin Increases Beta-Catenin Level through Protein Kinase A Activation and Regulates OPG Expression in Rat Primary Osteoblasts. International Journal of Endocrinology. 2015. Vol. 2015, no. 2015, pp.1-10.
https://search.emarefa.net/detail/BIM-1065743
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1065743