Oncostatin M stimulates prostaglandin D2-induced osteoprotegerin and interleukin-6 synthesis in osteoblasts. (May 2023)

• Record Type: Journal Article
• Authors: Kuroyanagi, Gen; Hioki, Tomoyuki; Tachi, Junko; Matsushima-Nishiwaki, Rie; Iida, Hiroki; Kozawa, Osamu; Tokuda, Haruhiko
• Is Part Of: Prostaglandins, leukotrienes, and essential fatty acids. Volume 192(2023)
• Publication Date: 2023-05
• Subjects: Oncostatin M -- Prostaglandin D2 -- Osteoprotegerin -- Interleukin-6 -- Osteal macrophage -- Osteoblast; Lipids -- Periodicals; Unsaturated fatty acids -- Periodicals; Prostaglandins -- Periodicals; Leukotrienes -- Periodicals; Fatty Acids, Unsaturated -- Periodicals; Acides gras insaturés -- Périodiques; Prostaglandines -- Périodiques; Leucotriènes -- Périodiques; Lipides -- Périodiques; 612.01577
• DOI: 10.1016/j.plefa.2023.102575
• Languages: English
• ISSNs: 0952-3278

Abstract

Highlights: Oncostatin M produced by osteal macrophages plays a significant role in bone remodeling and fracture healing. The effects of oncostatin M on the PGD2 -stimulated OPG and IL-6 synthesis in osteoblast-like MC3T3-E1 cells and normal human osteoblasts were investigated. Oncostatin M significantly increased the PGD2 -stimulated OPG and IL-6 release and mRNA expression levels in osteoblasts. Oncostatin M did not affect the phosphorylation of p38 MAP kinase, SAPK/JNK, and p44/p42 MAP kinase. Abstract: Oncostatin M produced by osteal macrophages plays a significant role in fracture healing. Osteoprotegerin (OPG) secreted by osteoblasts, binds to the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) as a decoy receptor and prevents RANKL from binding to RANK, resulting in bone resorption suppression. Interleukin-6 (IL-6) is a pro-inflammatory cytokine and generally regulates bone resorption. However, accumulating evidence suggests that IL-6 plays pivotal roles in bone formation. We previously showed that prostaglandin D2 (PGD2 ) induces OPG synthesis by activating p38 mitogen-activated protein (MAP) kinase, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. Furthermore, we demonstrated that PGD2 stimulates IL-6 synthesis by activating p38 MAP kinase and p44/p42 MAP kinase in MC3T3-E1 cells. In the present study, we investigated whether oncostatin M affects PGD2 -stimulated OPG and IL-6 synthesis in MC3T3-E1 cells through MAP kinase activation. The osteoblast-like MC3T3-E1 cells and normal human osteoblasts were treated with oncostatin M and subsequently stimulated with PGD2 . Consequently, oncostatin M significantly increased the PGD2 -stimulated OPG and IL-6 release in both cells. Oncostatin M significantly enhanced mRNA expression levels of OPG and IL-6 induced by PGD2 similarly in both cells. Regarding the signaling mechanism, oncostatin M did not affect the phosphorylation of p38 MAP kinase, SAPK/JNK, and p44/p42 MAP kinase. Our results suggest that oncostatin M upregulates the PGD2 -stimulated OPG and IL-6 synthesis in osteoblasts and therefore affects bone remodeling. However, OPG and IL-6 synthesis are not mediated through p38 MAP kinase, p44/p42 MAP kinase, or SAPK/JNK pathways.