Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
February-2016 Volume 37 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
February-2016 Volume 37 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

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

  • Authors:
    • Gen Kuroyanagi
    • Takanobu Otsuka
    • Naohiro Yamamoto
    • Shingo Kainuma
    • Reou Ohguchi
    • Kazuhiko Fujita
    • Rie Matsushima-Nishiwaki
    • Osamu Kozawa
    • Haruhiko Tokuda
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
  • Pages: 533-541
    |
    Published online on: January 7, 2016
       https://doi.org/10.3892/ijmm.2016.2452
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



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.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

View References

1 

Karsenty G and Wagner EF: Reaching a genetic and molecular understanding of skeletal development. Dev Cell. 2:389–406. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Parfitt AM: Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone. 30:5–7. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, et al: Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 89:309–319. 1997. View Article : Google Scholar : PubMed/NCBI

4 

Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G, Itie A, et al: OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 397:315–323. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Mizuno A, Amizuka N, Irie K, Murakami A, Fujise N, Kanno T, Sato Y, Nakagawa N, Yasuda H, Mochizuki S, et al: Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem Biophys Res Commun. 247:610–615. 1998. View Article : Google Scholar : PubMed/NCBI

6 

Kwan Tat S, Padrines M, Théoleyre S, Heymann D and Fortun Y: IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev. 15:49–60. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Hikiji H, Takato T, Shimizu T and Ishii S: The roles of prostanoids, leukotrienes, and platelet-activating factor in bone metabolism and disease. Prog Lipid Res. 47:107–126. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Blackwell KA, Raisz LG and Pilbeam CC: Prostaglandins in bone: bad cop, good cop? Trends Endocrinol Metab. 21:294–301. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Agas D, Marchetti L, Hurley MM and Sabbieti MG: Prostaglandin F2α: a bone remodeling mediator. J Cell Physiol. 228:25–29. 2013. View Article : Google Scholar

10 

Kuroyanagi G, Tokuda H, Matsushima-Nishiwaki R, Kondo A, Mizutani J, Kozawa O and Otsuka T: Resveratrol suppresses prostaglandin F2α-induced osteoprotegerin synthesis in osteoblasts: inhibition of the MAP kinase signaling. Arch Biochem Biophys. 542:39–45. 2014. View Article : Google Scholar

11 

Hirano T: Revisiting the 1986 molecular cloning of interleukin 6. Front Immunol. 5:4562014. View Article : Google Scholar : PubMed/NCBI

12 

Franchimont N, Wertz S and Malaise M: Interleukin-6: an osteotropic factor influencing bone formation? Bone. 37:601–606. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Tokuda H, Kozawa O, Harada A and Uematsu T: p42/p44 mitogen-activated protein kinase activation is involved in prostaglandin F2α-induced interleukin-6 synthesis in osteoblasts. Cell Signal. 11:325–330. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Minamitani C, Otsuka T, Takai S, Matsushima-Nishiwaki R, Adachi S, Hanai Y, Mizutani J, Tokuda H and Kozawa O: Involvement of Rho-kinase in prostaglandin F2α-stimulated interleukin-6 synthesis via p38 mitogen-activated protein kinase in osteoblasts. Mol Cell Endocrinol. 291:27–32. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Warnecke C, Griethe W, Weidemann A, Jürgensen JS, Willam C, Bachmann S, Ivashchenko Y, Wagner I, Frei U, Wiesener M and Eckardt KU: Activation of the hypoxia-inducible factor-pathway and stimulation of angiogenesis by application of prolyl hydroxylase inhibitors. FASEB J. 17:1186–1188. 2003.PubMed/NCBI

16 

Schofield CJ and Ratcliffe PJ: Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol. 5:343–354. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Knowles HJ, Cleton-Jansen AM, Korsching E and Athanasou NA: Hypoxia-inducible factor regulates osteoclast-mediated bone resorption: role of angiopoietin-like 4. FASEB J. 24:4648–4659. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Wang Y, Wan C, Deng L, Liu X, Cao X, Gilbert SR, Bouxsein ML, Faugere MC, Guldberg RE, Gerstenfeld LC, et al: The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest. 117:1616–1626. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Wan C, Gilbert SR, Wang Y, Cao X, Shen X, Ramaswamy G, Jacobsen KA, Alaql ZS, Eberhardt AW, Gerstenfeld LC, et al: Activation of the hypoxia-inducible factor-1α pathway accelerates bone regeneration. Proc Natl Acad Sci USA. 105:686–691. 2008. View Article : Google Scholar

20 

Sudo H, Kodama HA, Amagai Y, Yamamoto S and Kasai S: In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria. J Cell Biol. 96:191–198. 1983. View Article : Google Scholar : PubMed/NCBI

21 

Kozawa O, Tokuda H, Miwa M, Kotoyori J and Oiso Y: Cross-talk regulation between cyclic AMP production and phosphoinositide hydrolysis induced by prostaglandin E2 in osteoblast-like cells. Exp Cell Res. 198:130–134. 1992. View Article : Google Scholar : PubMed/NCBI

22 

Simpson DA, Feeney S, Boyle C and Stitt AW: Retinal VEGF mRNA measured by SYBR green I fluorescence: a versatile approach to quantitative PCR. Mol Vis. 6:178–183. 2000.PubMed/NCBI

23 

Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 227:680–685. 1970. View Article : Google Scholar : PubMed/NCBI

24 

Kato K, Ito H, Hasegawa K, Inaguma Y, Kozawa O and Asano T: Modulation of the stress-induced synthesis of hsp27 and alpha B-crystallin by cyclic AMP in C6 rat glioma cells. J Neurochem. 66:946–950. 1996. View Article : Google Scholar : PubMed/NCBI

25 

Shen X, Wan C, Ramaswamy G, Mavalli M, Wang Y, Duvall CL, Deng LF, Guldberg RE, Eberhart A, Clemens TL and Gilbert SR: Prolyl hydroxylase inhibitors increase neoangiogenesis and callus formation following femur fracture in mice. J Orthop Res. 27:1298–1305. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Donneys A, Deshpande SS, Tchanque-Fossuo CN, Johnson KL, Blough JT, Perosky JE, Kozloff KM, Felice PA, Nelson NS, Farberg AS, et al: Deferoxamine expedites consolidation during mandibular distraction osteogenesis. Bone. 55:384–390. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Fan L, Li J, Yu Z, Dang X and Wang K: The hypoxia-inducible factor pathway, prolyl hydroxylase domain protein inhibitors, and their roles in bone repair and regeneration. BioMed Res Int. 2014:2393562014. View Article : Google Scholar : PubMed/NCBI

28 

Kyriakis JM and Avruch J: Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 81:807–869. 2001.PubMed/NCBI

29 

Widmann C, Gibson S, Jarpe MB and Johnson GL: Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev. 79:143–180. 1999.PubMed/NCBI

30 

Erlebacher A, Filvaroff EH, Gitelman SE and Derynck R: Toward a molecular understanding of skeletal development. Cell. 80:371–378. 1995. View Article : Google Scholar : PubMed/NCBI

31 

Zelzer E and Olsen BR: Multiple roles of vascular endothelial growth factor (VEGF) in skeletal development, growth, and repair. Curr Top Dev Biol. 65:169–187. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kuroyanagi G, Otsuka T, Yamamoto N, Kainuma S, Ohguchi R, Fujita K, Matsushima-Nishiwaki R, Kozawa O and Tokuda H: Mimosine suppresses the PGF2α-induced synthesis of osteoprotegerin but not interleukin-6 in osteoblasts. Int J Mol Med 37: 533-541, 2016.
APA
Kuroyanagi, G., Otsuka, T., Yamamoto, N., Kainuma, S., Ohguchi, R., Fujita, K. ... Tokuda, H. (2016). Mimosine suppresses the PGF2α-induced synthesis of osteoprotegerin but not interleukin-6 in osteoblasts. International Journal of Molecular Medicine, 37, 533-541. https://doi.org/10.3892/ijmm.2016.2452
MLA
Kuroyanagi, G., Otsuka, T., Yamamoto, N., Kainuma, S., Ohguchi, R., Fujita, K., Matsushima-Nishiwaki, R., Kozawa, O., Tokuda, H."Mimosine suppresses the PGF2α-induced synthesis of osteoprotegerin but not interleukin-6 in osteoblasts". International Journal of Molecular Medicine 37.2 (2016): 533-541.
Chicago
Kuroyanagi, G., Otsuka, T., Yamamoto, N., Kainuma, S., Ohguchi, R., Fujita, K., Matsushima-Nishiwaki, R., Kozawa, O., Tokuda, H."Mimosine suppresses the PGF2α-induced synthesis of osteoprotegerin but not interleukin-6 in osteoblasts". International Journal of Molecular Medicine 37, no. 2 (2016): 533-541. https://doi.org/10.3892/ijmm.2016.2452
Copy and paste a formatted citation
x
Spandidos Publications style
Kuroyanagi G, Otsuka T, Yamamoto N, Kainuma S, Ohguchi R, Fujita K, Matsushima-Nishiwaki R, Kozawa O and Tokuda H: Mimosine suppresses the PGF2α-induced synthesis of osteoprotegerin but not interleukin-6 in osteoblasts. Int J Mol Med 37: 533-541, 2016.
APA
Kuroyanagi, G., Otsuka, T., Yamamoto, N., Kainuma, S., Ohguchi, R., Fujita, K. ... Tokuda, H. (2016). Mimosine suppresses the PGF2α-induced synthesis of osteoprotegerin but not interleukin-6 in osteoblasts. International Journal of Molecular Medicine, 37, 533-541. https://doi.org/10.3892/ijmm.2016.2452
MLA
Kuroyanagi, G., Otsuka, T., Yamamoto, N., Kainuma, S., Ohguchi, R., Fujita, K., Matsushima-Nishiwaki, R., Kozawa, O., Tokuda, H."Mimosine suppresses the PGF2α-induced synthesis of osteoprotegerin but not interleukin-6 in osteoblasts". International Journal of Molecular Medicine 37.2 (2016): 533-541.
Chicago
Kuroyanagi, G., Otsuka, T., Yamamoto, N., Kainuma, S., Ohguchi, R., Fujita, K., Matsushima-Nishiwaki, R., Kozawa, O., Tokuda, H."Mimosine suppresses the PGF2α-induced synthesis of osteoprotegerin but not interleukin-6 in osteoblasts". International Journal of Molecular Medicine 37, no. 2 (2016): 533-541. https://doi.org/10.3892/ijmm.2016.2452
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team