Gallein increases prostaglandin F2&alpha;‑induced osteoprotegerin and IL‑6 secretion in osteoblasts

Kuroyanagi,Gen; Hioki,Tomoyuki; Matsushima‑Nishiwaki,Rie; Omura,Takuya; Kozawa,Osamu; Tokuda,Haruhiko

doi:10.3892/br.2024.1835

Gallein increases prostaglandin F2α‑induced osteoprotegerin and IL‑6 secretion in osteoblasts

Authors:
- Gen Kuroyanagi
- Tomoyuki Hioki
- Rie Matsushima‑Nishiwaki
- Takuya Omura
- Osamu Kozawa
- Haruhiko Tokuda
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Affiliations: Department of Orthopedic Surgery, Nagoya City University, Nagoya 467‑8601, Japan, Department of Pharmacology, Gifu University, Gifu 501‑1194, Japan, Department of Metabolic Research, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi 474‑8511, Japan
Published online on: August 14, 2024 https://doi.org/10.3892/br.2024.1835
Article Number: 147

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Abstract

Gallein is a known Gβγ subunit inhibitor, but its function in bone metabolism, especially in osteoblasts, and its molecular mechanism remains to be elucidated. Osteoprotegerin (OPG), which is secreted from osteoblasts, binds to nuclear factor kB receptor activator (RANK) ligand (RANKL) as a decoy receptor, prevents RANKL‑RANK binding, and inhibits bone resorption. IL‑6 is not only a bone resorption factor but also as a bone metabolism regulator. Prostaglandin F2α (PGF2α) promotes p44/p42 MAPK, p38 MAPK and stress‑activated protein kinase/JNK phosphorylation in osteoblast‑like MC3T3‑E1 cells. In MC3T3‑E1 cells, activated p44/p42 and p38 MAPKs promote IL‑6 secretion and activated p44/p42 and p38 MAPKs and JNK promote OPG secretion. The present study aimed to investigate the effect and mechanism of gallein on PGF2α‑induced OPG and IL‑6 secretion using an osteoblastic MC3T3‑E1 cell line. It was found that gallein significantly increased PGF2α‑induced OPG and IL‑6 secretion in the MC3T3‑E1 cell. By contrast, fluorescein, which is a gallein‑like compound that does not bind to Gβγ, did not affect PGF2α‑induced OPG and IL‑6 secretion. Gallein significantly improved the PGF2α‑induced OPG and IL‑6 mRNA expression levels. Gallein did not affect the PGF2α‑activated phosphorylation of p44/p42 and p38 MAPKs and JNK. Gallein increased PGF2α‑induced OPG and IL‑6 secretion in osteoblasts, indicating that gallein may regulate bone remodeling via OPG/IL‑6 in bone metabolism.

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