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Melittin inhibits osteoclast formation through the downregulation of the RANKL-RANK signaling pathway and the inhibition of interleukin-1β in murine macrophages

  • Authors:
    • Jung-Yoon Choe
    • Seong-Kyu Kim
  • View Affiliations / Copyright

    Affiliations: Division of Rheumatology, Department of Internal Medicine, Arthritis and Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea
    Copyright: © Choe et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 539-548
    |
    Published online on: February 3, 2017
       https://doi.org/10.3892/ijmm.2017.2876
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Abstract

Melittin is a major toxic component of bee venom (Apis mellifera). It is not known whether melittin is involved in bone metabolism and osteoclastogenesis. The aim of this study was to determine the role of melittin in the regulation of osteoclastogenesis. In vitro osteoclastogenesis assays were performed using mouse RAW 264.7 cells and bone marrow-derived macrophages (BMMs) treated with receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Morphologic and functional analyses for osteoclast-like multinucleated cells (MNCs) were performed by tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and pit formation methods. The gene expression of TRAP, cathepsin K, matrix metalloproteinase-9 (MMP-9) and carbonic anhydrase II was measured by reverse transcription-quantitative PCR. The protein expression levels of mitogen-activated protein kinases (MAPKs), the p65 subunit of nuclear factor-κB (NF-κB), c-Fos, c-Jun, nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), TNF receptor-associated factor-6 (TRAF6), and interleukin-1β (IL-1β) were assessed by western blot analysis. Melittin inhibited the mRNA expression of TRAP, cathepsin K, MMP-9 and carbonic anhydrase II in RANKL-stimulated RAW 264.7 cells. The increased protein expression of TRAF6, p-extracellular signal-regulated kinase (ERK), p-JNK, p-p65, p-c-Fos and NFATc1 induced by RANKL was significantly suppressed in the RAW 264.7 cells treated with melittin. A synergistic effect of IL-1β on the formation of RANKL-induced osteoclast-like MNCs was found in two experimental cells. The increased expression of IL-1β following the stimulation of RAW 264.7 cells with RANKL activated TRAF6, p-ERK, p-JNK, p-p65, p-c-Fos and NFATc1. These effects were attenuated by the downregulation of IL-1β using siRNA against IL-1β, and also by treatment with melittin. On the whole, the findings of this study demonstrate that melittin inhibits the formation of osteoclast-like MNCs by interfering with the RANKL-RANK signaling pathway.
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1 

Takayanagi H: Osteoimmunology: Shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol. 7:292–304. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Asagiri M and Takayanagi H: The molecular understanding of osteoclast differentiation. Bone. 40:251–264. 2007. View Article : Google Scholar

3 

Teitelbaum SL: Osteoclasts; culprits in inflammatory osteolysis. Arthritis Res Ther. 8:2012006. View Article : Google Scholar :

4 

Udagawa N, Kotake S, Kamatani N, Takahashi N and Suda T: The molecular mechanism of osteoclastogenesis in rheumatoid arthritis. Arthritis Res. 4:281–289. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Colucci S, Brunetti G, Cantatore FP, Oranger A, Mori G, Quarta L, Cirulli N, Mancini L, Corrado A, Grassi FR and Grano M: Lymphocytes and synovial fluid fibroblasts support osteoclastogenesis through RANKL, TNFα, and IL-7 in an in vitro model derived from human psoriatic arthritis. J Pathol. 212:47–55. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Dalbeth N, Smith T, Nicolson B, Clark B, Callon K, Naot D, Haskard DO, McQueen FM, Reid IR and Cornish J: Enhanced osteoclastogenesis in patients with tophaceous gout: Urate crystals promote osteoclast development through interactions with stromal cells. Arthritis Rheum (Munch). 58:1854–1865. 2008. View Article : Google Scholar

7 

Lee SJ, Nam KI, Jin HM, Cho YN, Lee SE, Kim TJ, Lee SS, Kee SJ, Lee KB, Kim N and Park YW: Bone destruction by receptor activator of nuclear factor κB ligand-expressing T cells in chronic gouty arthritis. Arthritis Res Ther. 13:R1642011. View Article : Google Scholar

8 

Gowen M, Wood DD, Ihrie EJ, Meats JE and Russell RG: Stimulation by human interleukin 1 of cartilage breakdown and production of collagenase and proteoglycanase by human chondrocytes but not by human osteoblasts in vitro. BBA. 797:186–193. 1984.PubMed/NCBI

9 

Kim JH, Jin HM, Kim K, Song I, Youn BU, Matsuo K and Kim N: The mechanism of osteoclast differentiation induced by IL-1. J Immunol. 183:1862–1870. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Wei S, Kitaura H, Zhou P, Ross FP and Teitelbaum SL: IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest. 115:282–290. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Strand V and Kavanaugh AF: The role of interleukin-1 in bone resorption in rheumatoid arthritis. Rheumatology (Oxford). 43(Suppl 3): iii10–iii16. 2004. View Article : Google Scholar

12 

Billingham ME, Morley J, Hanson JM, Shipolini RA and Vernon CA: Letter: An anti-inflammatory peptide from bee venom. Nat Lett. 245:163–164. 1973. View Article : Google Scholar

13 

Kwon YB, Lee HJ, Han HJ, Mar WC, Kang SK, Yoon OB, Beitz AJ and Lee JH: The water-soluble fraction of bee venom produces antinociceptive and anti-inflammatory effects on rheumatoid arthritis in rats. Life Sci. 71:191–204. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Park HJ, Lee SH, Son DJ, Oh KW, Kim KH, Song HS, Kim GJ, Oh GT, Yoon DY and Hong JT: Antiarthritic effect of bee venom: Inhibition of inflammation mediator generation by suppression of NF-κB through interaction with the p50 subunit. Arthritis Rheum (Munch). 35:3504–3515. 2004. View Article : Google Scholar

15 

Terwilliger JT and Eisenberg D: The structure of melittin. II. Interpretation of the structure. J Biol Chem. 257:6016–6022. 1982.PubMed/NCBI

16 

Kim SK, Park KY, Yoon WC, Park SH, Park KK, Yoo DH and Choe JY: Melittin enhances apoptosis through suppression of IL-6/sIL-6R complex-induced NF-κB and STAT3 activation and Bcl-2 expression for human fibroblast-like synoviocytes in rheumatoid arthritis. Joint Bone Spine. 78:471–477. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Tashjian AH Jr, Ivey JL, Delclos B and Levine L: Stimulation of prostaglandin production in bone by phorbol diesters and melittin. Prostaglandins. 16:221–232. 1978. View Article : Google Scholar : PubMed/NCBI

18 

Park H, Jung YK, Park OJ, Lee YJ, Choi JY and Choi Y: Interaction of Fas ligand and Fas expressed on osteoclast precursors increases osteoclastogenesis. J Immunol. 175:7193–7201. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Lee JD, Kim SY, Kim TW, Lee SH, Yang HI, Lee DI and Lee YH: Anti-inflammatory effect of bee venom on type II collagen-induced arthritis. Am J Chin Med. 32:361–367. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Naito A, Azuma S, Tanaka S, Miyazaki T, Takaki S, Takatsu K, Nakao K, Nakamura K, Katsuki M, Yamamoto T and Inoue J: Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells. 4:353–362. 1999. View Article : Google Scholar : PubMed/NCBI

21 

Wei S, Teitelbaum SL, Wang MW and Ross FP: Receptor activator of nuclear factor-κB ligand activates nuclear factor-κB in osteoclast precursors. Endocrinology. 142:1290–1295. 2001.PubMed/NCBI

22 

Miyazaki T, Katagiri H, Kanegae Y, Takayanagi H, Sawada Y, Yamamoto A, Pando MP, Asano T, Verma IM, Oda H, et al: Reciprocal role of ERK and NF-κB pathways in survival and activation of osteoclasts. J Cell Biol. 148:333–342. 2000. View Article : Google Scholar : PubMed/NCBI

23 

David JP, Sabapathy K, Hoffmann O, Idarraga MH and Wagner EF: JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and -independent mechanisms. J Cell Sci. 115:4317–4325. 2002. View Article : Google Scholar : PubMed/NCBI

24 

Lee WR, Kim KH, An HJ, Kim JY, Chang YC, Chung H, Park YY, Lee ML and Park KK: The protective effects of melittin on Propionibacterium acnes-induced inflammatory responses in vitro and in vivo. J Invest Dermatol. 134:1922–1930. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Jimi E, Akiyama S, Tsurukai T, Okahashi N, Kobayashi K, Udagawa N, Nishihara T, Takahashi N and Suda T: Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function. J Immunol. 163:434–442. 1999.PubMed/NCBI

26 

Tanabe N, Maeno M, Suzuki N, Fujisaki K, Tanaka H, Ogiso B and Ito K: IL-1a stimulates the formation of osteoclast-like cells by increasing M-CSF and PGE2 production and decreasing OPG production by osteoblasts. Life Sci. 77:615–626. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Stuhlmeier KM: Apis mellifera venom and melittin block neither NF-κB-50-DNA interactions nor the activation of NF-κB, instead they activate the transcription of proinflammatory genes and the release of reactive oxygen intermediates. J Immunol. 179:655–664. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Choe J and Kim S: Melittin inhibits osteoclast formation through the downregulation of the RANKL-RANK signaling pathway and the inhibition of interleukin-1β in murine macrophages. Int J Mol Med 39: 539-548, 2017.
APA
Choe, J., & Kim, S. (2017). Melittin inhibits osteoclast formation through the downregulation of the RANKL-RANK signaling pathway and the inhibition of interleukin-1β in murine macrophages. International Journal of Molecular Medicine, 39, 539-548. https://doi.org/10.3892/ijmm.2017.2876
MLA
Choe, J., Kim, S."Melittin inhibits osteoclast formation through the downregulation of the RANKL-RANK signaling pathway and the inhibition of interleukin-1β in murine macrophages". International Journal of Molecular Medicine 39.3 (2017): 539-548.
Chicago
Choe, J., Kim, S."Melittin inhibits osteoclast formation through the downregulation of the RANKL-RANK signaling pathway and the inhibition of interleukin-1β in murine macrophages". International Journal of Molecular Medicine 39, no. 3 (2017): 539-548. https://doi.org/10.3892/ijmm.2017.2876
Copy and paste a formatted citation
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Spandidos Publications style
Choe J and Kim S: Melittin inhibits osteoclast formation through the downregulation of the RANKL-RANK signaling pathway and the inhibition of interleukin-1β in murine macrophages. Int J Mol Med 39: 539-548, 2017.
APA
Choe, J., & Kim, S. (2017). Melittin inhibits osteoclast formation through the downregulation of the RANKL-RANK signaling pathway and the inhibition of interleukin-1β in murine macrophages. International Journal of Molecular Medicine, 39, 539-548. https://doi.org/10.3892/ijmm.2017.2876
MLA
Choe, J., Kim, S."Melittin inhibits osteoclast formation through the downregulation of the RANKL-RANK signaling pathway and the inhibition of interleukin-1β in murine macrophages". International Journal of Molecular Medicine 39.3 (2017): 539-548.
Chicago
Choe, J., Kim, S."Melittin inhibits osteoclast formation through the downregulation of the RANKL-RANK signaling pathway and the inhibition of interleukin-1β in murine macrophages". International Journal of Molecular Medicine 39, no. 3 (2017): 539-548. https://doi.org/10.3892/ijmm.2017.2876
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