Horm Metab Res 2022; 54(01): 42-49
DOI: 10.1055/a-1713-7967
Endocrine Research

Incretins Enhance PGF-Induced Synthesis of IL-6 and Osteoprotegerin in Osteoblasts

Tomoyuki Hioki
1   Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
2   Department of Dermatology, Kizawa Memorial Hospital, Minokamo, Japan
,
1   Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
3   Department of Rehabilitation Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
4   Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
,
Kazuhiko Fujita
1   Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
4   Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
,
Go Sakai
1   Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
4   Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
,
Tetsu Kawabata
1   Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
4   Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
,
Woo Kim
1   Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
5   Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
,
Junko Tachi
1   Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
5   Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
,
Rie Matsushima-Nishiwaki
1   Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
,
Hiroki Iida
5   Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
,
1   Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
,
Haruhiko Tokuda
1   Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
6   Department of Clinical Laboratory/Biobank of Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Japan
› Author Affiliations
Funding Information Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan: 15K10487, 17K11002, 19K18471.

Abstract

Incretins including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), which are secreted from the small intestine after oral food ingestion, are currently well-known to stimulate insulin secretion from pancreatic β-cells and used for the treatment of type 2 diabetes mellitus. We have previously reported that prostaglandin F (PGF) stimulates the synthesis of interleukin-6 (IL-6) and osteoprotegerin in osteoblast-like MC3T3-E1 cells, and that IL-6 and osteoprotegerin release are mediated through the p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase or stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) pathways. In the present study, we investigated the effects of incretins including GLP-1 and GIP, on the PGF-induced synthesis of IL-6 and osteoprotegerin and examined the detailed mechanism in osteoblast-like MC3T3-E1 cells. We found that GIP and GLP-1 significantly stimulated the PGF-induced synthesis of IL-6 in osteoblast-like MC3T3-E1 cells. In addition, GIP and GLP-1 significantly enhanced the PGF-induced mRNA expression levels of IL-6. On the other hand, GIP and GLP-1 markedly stimulated the PGF-induced synthesis of osteoprotegerin. However, the phosphorylation of p44/p42 MAP kinase, p38 MAP kinase, or JNK induced by PGF was not affected by GIP or GLP-1. Therefore, these results strongly suggest that incretins enhance the PGF-induced synthesis of IL-6 and osteoprotegerin in osteoblast-like MC3T3-E1 cells. However, these syntheses are not mediated through p44/p42 MAP kinase, p38 MAP kinase, or JNK pathways.



Publication History

Received: 21 February 2021

Accepted after revision: 30 November 2021

Article published online:
05 January 2022

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