GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Ghrelin Increases Beta-Catenin Level through Protein Kinase A Activation and Regulates OPG Expression in Rat Primary Osteoblasts.
Mrak. Emanuela E; Casati. Lavinia L; Pagani. Francesca F; Rubinacci. Alessandro A; Zarattini. Guido G; Sibilia. Valeria V
Key Findings
- Ghrelin at very low doses raises β‑catenin levels in rat osteoblasts via the GHS‑R1a receptor.
- The rise in β‑catenin depends on protein kinase A (PKA) activity and inhibition of GSK‑3β.
- Ghrelin also increases osteoprotegerin (OPG) and lowers the RANKL/OPG ratio, which can suppress formation of bone‑resorbing osteoclasts.
Practical Outcomes
- For biohackers, the data hint that boosting ghrelin signaling might help maintain bone density, but the work is limited to rat cells and uses a hormone level far lower than typical supplement doses. No clear dosing or safety guidance for humans is provided, so the finding is more of a mechanistic clue than a ready‑to‑use protocol.
Summary
The study shows that ghrelin, a hormone that normally makes you feel hungry, can also boost bone‑building cells in rats by turning on a pathway (β‑catenin) and increasing a protein called OPG that blocks bone‑breaking cells. This effect needs the ghrelin receptor and is stopped by a specific blocker (D‑Lys(3)-GHRP‑6).
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(-10)M) 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-Lys(3)-GHRP-6 (10(-7)M). 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-Lys(3)-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.
Study Information
pubmed
2015
2015-03-17T00:00:00.000Z
10.1155/2015/547473
15
46