Mimosine suppresses the PGF2α-induced synthesis of osteoprotegerin but not interleukin-6 in osteoblasts.

Abstract

Mimosine, a plant amino acid, is known to act as a normoxic inducer of hypoxia-inducible factor (HIF). Previous research has suggested that HIF plays important roles in angiogenesis-osteogenesis coupling and bone metabolism. We previously reported that prostaglandin F2α (PGF2α) induced osteoprotegerin synthesis through p38 mitogen-activated protein (MAP) kinase, p44/p42 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. We have also demonstrated that PGF2α induced the synthesis of interleukin-6 (IL-6) via p38 MAP kinase and p44/p42 MAP kinase but not SAPK/JNK in these cells. In the present study, we investigated the effects of mimosine on the PGF2α-induced synthesis of osteoprotegerin or IL-6 in MC3T3-E1 cells. We found that deferoxamine, another inducer of HIF, as well as mimosine, upregulated the protein levels of HIF-1α. Both mimosine and deferoxamine significantly suppressed the PGF2α-induced release of osteoprotegerin, and the mRNA expression level, without markedly affecting PGF2α-induced IL-6 release. Both mimosine and deferoxamine, by themselves, induced the release of vascular endothelial growth factor. The phosphorylation of p38 MAP kinase, p44/p42 MAP kinase or SAPK/JNK induced by PGF2α was not markedly affected by either mimosine or deferoxamine. Thus, the results of the present study strongly suggest that mimosine, a normoxic inducer of HIF, inhibits the PGF2α‑induced osteoprotegerin synthesis without affecting the IL-6 synthesis in osteoblasts.

• Authors: Gen Kuroyanagi, Takanobu Otsuka, Naohiro Yamamoto, Shingo Kainuma, Reou Ohguchi, Kazuhiko Fujita, Rie Matsushima-Nishiwaki, Osamu Kozawa, Haruhiko Tokuda
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 37 Issue 2 Pg. 533-41 (Feb 2016) ISSN: 1791-244X [Electronic] Greece
• PMID: 26744072 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hypoxia-Inducible Factor 1
• Interleukin-6
• Osteoprotegerin
• Peptide Fragments
• RNA, Messenger
• Transcription Factors
• Tumor Suppressor Protein p53
• WDR77 protein, mouse
• Mimosine
• Dinoprost
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase 4
• Deferoxamine

Topics

• Animals
• Cell Differentiation (drug effects, genetics)
• Cell Line
• Deferoxamine (administration & dosage)
• Dinoprost (administration & dosage, metabolism)
• Gene Expression Regulation, Developmental (drug effects)
• Hypoxia-Inducible Factor 1 (biosynthesis)
• Interleukin-6 (biosynthesis, genetics)
• MAP Kinase Kinase 4 (biosynthesis)
• Mice
• Mimosine (administration & dosage)
• Osteoblasts (drug effects)
• Osteoprotegerin (biosynthesis, genetics)
• Peptide Fragments (biosynthesis)
• RNA, Messenger (biosynthesis)
• Transcription Factors
• Tumor Suppressor Protein p53 (biosynthesis)
• p38 Mitogen-Activated Protein Kinases (biosynthesis)