Cyclolinopeptide F, a Cyclic Peptide from Flaxseed Inhibited RANKL-induced Osteoclastogenesis Via Downergulation of RANK Expression

Overview

Journal J Nat Med

Publisher Springer

Date 2019 Mar 17

PMID 30877416

Citations 4

Authors

Toshio Kaneda

Yuki Nakajima

Sae Koshikawa

Alfarius Eko Nugroho

Hiroshi Morita

Affiliations

Soon will be listed here.

Abstract

Previously, we reported that cyclolinopeptides (CLs) extracted from flaxseed inhibited receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclastogenesis from mouse bone marrow cells in vitro. However, mode of action involved in CLs-inhibited osteoclastogenesis has been yet unknown. Therefore, in this study, we investigated the details of inhibitory activity of cyclolinopeptide-F (CL-F) in osteoclastogenesis, as a representative of CLs. CL-F dose-dependently inhibited RANKL-induced osteoclastogenesis (IC 0.58 µM) without cytotoxic effects. The inhibition by CL-F was mainly observed in macrophage colony-stimulating factor (M-CSF)-induced proliferation/differentiation phase from M-CSF responsive immature myeloid cells to monocyte/macrophage (M/Mϕ) lineage. Additionally, CL-F also slightly inhibited RANKL-induced differentiation phase from M/Mϕ to mature osteoclasts. Expression of RANKL receptor, RANK, in M-CSF-induced M/Mϕ, i.e. osteoclast progenitor cells, was decreased by CL-F treatment. Furthermore, RT-PCR analysis revealed that CL-F inhibited c-fos gene expression, which is reported to be crucial for RANK expression in osteoclast progenitor cells induced with M-CSF from myeloid lineage cells. These results suggested that CL-F inhibits osteoclastogenesis via down regulation of c-fos expression, which leads to the down-regulation of RANK expression in M-CSF-induced osteoclast progenitors.

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References

Rietjens I, Louisse J, Beekmann K . The potential health effects of dietary phytoestrogens. Br J Pharmacol. 2016; 174(11):1263-1280. PMC: 5429336. DOI: 10.1111/bph.13622. View

Kong Y, Yoshida H, Sarosi I, Tan H, Timms E, Capparelli C . OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999; 397(6717):315-23. DOI: 10.1038/16852. View

Takayanagi H . Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol. 2007; 7(4):292-304. DOI: 10.1038/nri2062. View

Sherr C . Colony-stimulating factor-1 receptor. Blood. 1990; 75(1):1-12. View

Arai A, Mizoguchi T, Harada S, Kobayashi Y, Nakamichi Y, Yasuda H . Fos plays an essential role in the upregulation of RANK expression in osteoclast precursors within the bone microenvironment. J Cell Sci. 2012; 125(Pt 12):2910-7. DOI: 10.1242/jcs.099986. View

Kaneda T, Yoshida H, Nakajima Y, Toishi M, Nugroho A, Morita H . Cyclolinopeptides, cyclic peptides from flaxseed with osteoclast differentiation inhibitory activity. Bioorg Med Chem Lett. 2016; 26(7):1760-1. DOI: 10.1016/j.bmcl.2016.02.040. View

Wiktor-Jedrzejczak W, Bartocci A, Ferrante Jr A, Ahmed-Ansari A, Sell K, Pollard J . Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. Proc Natl Acad Sci U S A. 1990; 87(12):4828-32. PMC: 54211. DOI: 10.1073/pnas.87.12.4828. View

Glazier M, Bowman M . A review of the evidence for the use of phytoestrogens as a replacement for traditional estrogen replacement therapy. Arch Intern Med. 2001; 161(9):1161-72. DOI: 10.1001/archinte.161.9.1161. View

Schmidt T, Klaes M, Sendker J . Lignans in seeds of Linum species. Phytochemistry. 2012; 82:89-99. DOI: 10.1016/j.phytochem.2012.07.004. View

10.

Wang Y, Xu Z, Yang D, Yao H, Ku B, Ma X . The antidepressant effect of secoisolariciresinol, a lignan-type phytoestrogen constituent of flaxseed, on ovariectomized mice. J Nat Med. 2012; 67(1):222-7. DOI: 10.1007/s11418-012-0655-x. View

11.

Matsuo K, Owens J, Tonko M, Elliott C, Chambers T, Wagner E . Fosl1 is a transcriptional target of c-Fos during osteoclast differentiation. Nat Genet. 2000; 24(2):184-7. DOI: 10.1038/72855. View

12.

Boyle W, Simonet W, Lacey D . Osteoclast differentiation and activation. Nature. 2003; 423(6937):337-42. DOI: 10.1038/nature01658. View

13.

Rodan G, Martin T . Therapeutic approaches to bone diseases. Science. 2000; 289(5484):1508-14. DOI: 10.1126/science.289.5484.1508. View

14.

Raghavan A, Robison R, McNabb J, Miller C, Williams D, Bohjanen P . HuA and tristetraprolin are induced following T cell activation and display distinct but overlapping RNA binding specificities. J Biol Chem. 2001; 276(51):47958-65. DOI: 10.1074/jbc.M109511200. View

15.

Kaneda T, Nojima T, Nakagawa M, Ogasawara A, Kaneko H, Sato T . Endogenous production of TGF-beta is essential for osteoclastogenesis induced by a combination of receptor activator of NF-kappa B ligand and macrophage-colony-stimulating factor. J Immunol. 2000; 165(8):4254-63. DOI: 10.4049/jimmunol.165.8.4254. View

16.

Yoshida H, Hayashi S, Kunisada T, Ogawa M, Okamura H, Sudo T . The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature. 1990; 345(6274):442-4. DOI: 10.1038/345442a0. View

17.

Matsumoto T, Shishido A, Morita H, Itokawa H, Takeya K . Cyclolinopeptides F-I, cyclic peptides from linseed. Phytochemistry. 2001; 57(2):251-60. DOI: 10.1016/s0031-9422(00)00442-8. View

18.

Takayanagi H, Kim S, Matsuo K, Suzuki H, Suzuki T, Sato K . RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta. Nature. 2002; 416(6882):744-9. DOI: 10.1038/416744a. View

19.

Janckila A, Takahashi K, Sun S, Yam L . Naphthol-ASBI phosphate as a preferred substrate for tartrate-resistant acid phosphatase isoform 5b. J Bone Miner Res. 2001; 16(4):788-93. DOI: 10.1359/jbmr.2001.16.4.788. View

20.

Hayashi T, Kaneda T, Toyama Y, Kumegawa M, Hakeda Y . Regulation of receptor activator of NF-kappa B ligand-induced osteoclastogenesis by endogenous interferon-beta (INF-beta ) and suppressors of cytokine signaling (SOCS). The possible counteracting role of SOCSs- in IFN-beta-inhibited osteoclast.... J Biol Chem. 2002; 277(31):27880-6. DOI: 10.1074/jbc.M203836200. View