Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Oncostatin M Suppresses Bone Morphogenetic Protein-4-Induced Osteoprotegerin Synthesis in Osteoblasts: Attenuation of p70 S6 Kinase

Version 1 : Received: 31 December 2023 / Approved: 2 January 2024 / Online: 2 January 2024 (09:38:17 CET)

How to cite: Hioki, T.; Tachi, J.; Matsushima-Nishiwaki, R.; Iida, H.; Kozawa, O.; Tokuda, H. Oncostatin M Suppresses Bone Morphogenetic Protein-4-Induced Osteoprotegerin Synthesis in Osteoblasts: Attenuation of p70 S6 Kinase. Preprints 2024, 2024010053. https://doi.org/10.20944/preprints202401.0053.v1 Hioki, T.; Tachi, J.; Matsushima-Nishiwaki, R.; Iida, H.; Kozawa, O.; Tokuda, H. Oncostatin M Suppresses Bone Morphogenetic Protein-4-Induced Osteoprotegerin Synthesis in Osteoblasts: Attenuation of p70 S6 Kinase. Preprints 2024, 2024010053. https://doi.org/10.20944/preprints202401.0053.v1

Abstract

Oncostatin M (OSM), an inflammatory cytokine belonging to interleukin-6 superfamily, is recognized as an essential factor secreted by osteal macrophages to orchestrate bone remodelling. Osteoprotegerin (OPG) produced by osteoblasts regulates osteoclastogenesis. We previously demonstrated that bone morphogenetic protein-4 (BMP-4) stimulates OPG synthesis in osteoblast-like MC3T3-E1 cells, and that SMAD1/5/8(9), p38 mitogen-activated protein kinase (MAPK), and p70 S6 kinase positively regulates the OPG synthesis. The present study is aimed to investigate the effect of OSM on BMP-4-stimulated OPG synthesis in osteoblasts. OSM suppressed the release and the mRNA expression of OPG upregulated by BMP-4 in MC3T3-E1 cells.  Neither the BMP-4-induced phosphorylation of SMAD1/5/9 nor that of p38 MAPK affected by OSM. On the other hand, the BMP-4-stimulated phosphorylation of p70 S6 kinase was considerably suppressed by OSM. These results strongly suggest that OSM suppresses the BMP-4-stimulated OPG synthesis via inhibition of the p70 S6 kinase-mediated pathway in osteoblasts.

Keywords

oncostatin M; bone morphogenetic protein-4; osteoprotegerin; p70 S6 kinase; osteoblast

Subject

Biology and Life Sciences, Endocrinology and Metabolism

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