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Article

Oncostatin M enhances osteoprotegerin synthesis but reduces macrophage colony‑stimulating factor synthesis in bFGF‑stimulated osteoblast‑like cells

  • Authors:
    • Tomoyuki Hioki
    • Junko Tachi
    • Kyohei Ueda
    • Rie Matsushima‑Nishiwaki
    • Hiroki Iida
    • Osamu Kozawa
    • Haruhiko Tokuda
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan, Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan
  • Article Number: 34
    |
    Published online on: November 24, 2023
       https://doi.org/10.3892/etm.2023.12322
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Abstract

Bone remodeling is tightly controlled by various factors, including hormones, autacoids and cytokines. Among them, oncostatin M (OSM) is a multifunctional cytokine produced by osteal macrophages, which serves as an essential modulator of bone remodeling. Macrophage colony‑stimulating factor (M‑CSF) and osteoprotegerin are secreted by osteoblasts, and also have pivotal roles in the regulation of the bone remodeling process. The binding of basic fibroblast growth factor (bFGF), a key regulator of bone remodeling, to the corresponding receptor [fibroblast growth factor receptor (FGFR)] triggers the dimerization and activation of FGFRs, which causes the phosphorylation of FGFR substrates and subsequent activation of downstream effectors, including mitogen‑activated protein kinases (MAPKs), via Grb2. bFGF can activate MAPKs, resulting in the synthesis of osteoprotegerin and vascular endothelial growth factor in osteoblast‑like MC3T3‑E1 cells. In the present study, the effects of OSM on bFGF‑induced osteoblast activation were investigated in the synthesis of osteoprotegerin and M‑CSF in osteoblasts. The release of osteoprotegerin and M‑CSF were analyzed using ELISA. The mRNA expression levels of osteoprotegerin and M‑CSF were analyzed using reverse transcription‑quantitative PCR. Phosphorylation of p38 MAPK, stress‑activated protein kinase/c‑Jun N‑terminal kinase (SAPK/JNK) and p44/p42 MAPK was assessed using western blotting. OSM enhanced bFGF‑induced osteoprotegerin release and bFGF‑stimulated mRNA expression of osteoprotegerin. By contrast, OSM suppressed the bFGF‑induced release of M‑CSF and bFGF‑stimulated mRNA expression of M‑CSF. SB203580, a p38 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, suppressed the bFGF‑stimulated M‑CSF release, whereas PD98059, an upstream kinase inhibitor of p44/p42 MAPK, failed to suppress the M‑CSF release stimulated by bFGF. Furthermore, OSM enhanced the bFGF‑induced phosphorylation of p38 MAPK, but attenuated the bFGF‑stimulated phosphorylation of SAPK/JNK. By contrast, OSM had little effect on the bFGF‑induced phosphorylation of p44/p42 MAPK. SB203580 markedly reduced the amplification of bFGF‑stimulated osteoprotegerin release enhanced by OSM. These results strongly suggested that OSM may possess divergent effects on bFGF‑induced osteoblast activation, upregulation of p38 MAPK and downregulation of SAPK/JNK, leading to the amplification of osteoprotegerin synthesis and the attenuation of M‑CSF synthesis.
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Copy and paste a formatted citation
Spandidos Publications style
Hioki T, Tachi J, Ueda K, Matsushima‑Nishiwaki R, Iida H, Kozawa O and Tokuda H: Oncostatin M enhances osteoprotegerin synthesis but reduces macrophage colony‑stimulating factor synthesis in bFGF‑stimulated osteoblast‑like cells. Exp Ther Med 27: 34, 2024.
APA
Hioki, T., Tachi, J., Ueda, K., Matsushima‑Nishiwaki, R., Iida, H., Kozawa, O., & Tokuda, H. (2024). Oncostatin M enhances osteoprotegerin synthesis but reduces macrophage colony‑stimulating factor synthesis in bFGF‑stimulated osteoblast‑like cells. Experimental and Therapeutic Medicine, 27, 34. https://doi.org/10.3892/etm.2023.12322
MLA
Hioki, T., Tachi, J., Ueda, K., Matsushima‑Nishiwaki, R., Iida, H., Kozawa, O., Tokuda, H."Oncostatin M enhances osteoprotegerin synthesis but reduces macrophage colony‑stimulating factor synthesis in bFGF‑stimulated osteoblast‑like cells". Experimental and Therapeutic Medicine 27.1 (2024): 34.
Chicago
Hioki, T., Tachi, J., Ueda, K., Matsushima‑Nishiwaki, R., Iida, H., Kozawa, O., Tokuda, H."Oncostatin M enhances osteoprotegerin synthesis but reduces macrophage colony‑stimulating factor synthesis in bFGF‑stimulated osteoblast‑like cells". Experimental and Therapeutic Medicine 27, no. 1 (2024): 34. https://doi.org/10.3892/etm.2023.12322
Copy and paste a formatted citation
x
Spandidos Publications style
Hioki T, Tachi J, Ueda K, Matsushima‑Nishiwaki R, Iida H, Kozawa O and Tokuda H: Oncostatin M enhances osteoprotegerin synthesis but reduces macrophage colony‑stimulating factor synthesis in bFGF‑stimulated osteoblast‑like cells. Exp Ther Med 27: 34, 2024.
APA
Hioki, T., Tachi, J., Ueda, K., Matsushima‑Nishiwaki, R., Iida, H., Kozawa, O., & Tokuda, H. (2024). Oncostatin M enhances osteoprotegerin synthesis but reduces macrophage colony‑stimulating factor synthesis in bFGF‑stimulated osteoblast‑like cells. Experimental and Therapeutic Medicine, 27, 34. https://doi.org/10.3892/etm.2023.12322
MLA
Hioki, T., Tachi, J., Ueda, K., Matsushima‑Nishiwaki, R., Iida, H., Kozawa, O., Tokuda, H."Oncostatin M enhances osteoprotegerin synthesis but reduces macrophage colony‑stimulating factor synthesis in bFGF‑stimulated osteoblast‑like cells". Experimental and Therapeutic Medicine 27.1 (2024): 34.
Chicago
Hioki, T., Tachi, J., Ueda, K., Matsushima‑Nishiwaki, R., Iida, H., Kozawa, O., Tokuda, H."Oncostatin M enhances osteoprotegerin synthesis but reduces macrophage colony‑stimulating factor synthesis in bFGF‑stimulated osteoblast‑like cells". Experimental and Therapeutic Medicine 27, no. 1 (2024): 34. https://doi.org/10.3892/etm.2023.12322
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