Browse > Article
http://dx.doi.org/10.4062/biomolther.2011.19.1.070

Ethyl Docosahexaenoate and Its Acidic Form Increase Bone Formation by Induction of Osteoblast Differentiation and Inhibition of Osteoclastogenesis  

Choi, Bo-Yun (Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University)
Eun, Jae-Soon (College of Pharmacy, Woosuk University)
Nepal, Manoj (Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University)
Lee, Mi-Kyung (College of Pharmacy, Woosuk University)
Bae, Tae-Sung (Department of Dental Biomaterials, School of Dentistry, Chonbuk National University)
Kim, Byung-Il (Department of Materials Science and Metallurgical Engineering, Sunchon National University)
Soh, Yun-Jo (Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University)
Publication Information
Biomolecules & Therapeutics / v.19, no.1, 2011 , pp. 70-76 More about this Journal
Abstract
Bone remodeling is a dynamic process involving a constant balance between osteoclast-induced bone resorption and osteoblast-induced bone formation. Osteoclasts play a crucial homeostatic role in skeletal modeling and remodeling, and destroy bone in many pathological conditions. Previously, we reported that the hexane soluble fraction of Ficus carica inhibited osteoclast differentiation. Poly unsaturated fatty acids, such as ethyl docosahexaenoate (E-DHA), docosahexaenoic acid (DHA), cis-11,14-eicosadienoic acid (EDA) and eicosapentaenoic acid (EPA), were identified from the hexane soluble fraction of Ficus carica. Among them, E-DHA most potently inhibited osteoclastogenesis in RAW264.7 cells. E-DHA reduced the activities of JNK and NF-$\kappa}B$. E-DHA suppressed the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). Interestingly, DHA increased the activity of alkaline phosphatase and expression of bone morphogenetic protein 2 (BMP2) more than E-DHA in MC3T3-E1 cells, suggesting that DHA may induce osteoblast differentiation. The data suggests that a combination of E-DHA and DHA has potential use in the treatment of diseases involving abnormal bone lysis, such as osteoporosis, rheumatoid arthritis and periodontal bone erosion.
Keywords
Ethyl docosahexaenoate; Bone formation; RAW264.7 cells; MC3T3-E1 cells; Docosahexaenoic acid;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 0  (Related Records In Web of Science)
Times Cited By SCOPUS : 0
연도 인용수 순위
1 Tachi, K., Takami, M., Zhao, B., Mochizuki, A., Miyamoto, Y., Inoue, T., Baba, K. and Kamijo, R. (2010b) Bone morphogenetic protein 2 enhances mouse osteoclast differentiation via increased levels of receptor activator of $NF-{\kappa}B$ ligand expression in osteocblast. Cell Tissue Res. 342, 213-220.   DOI
2 Takayanagi, H., Kim, S., Koga, T., Nishina, H., Isshiki, M., Yoshida, H., Saiura, A., Isobe, M., Yokochi, T., Inoue, J., Wagner, E. F., Mak, T. W., Kodama, T. and Taniguchi, T. (2002) Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev. Cell 3, 889-901.   DOI
3 Luo, J. L., Kamata, H. and Karin, M. (2005) IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy. J. Clin. Invest. 115, 2625-2632.   DOI
4 Meydani, S. N., Endres, S., Woods, M. M., Goldin, B. R., Soo, C., Morrill-Labrode, A., Dinarello, C. A. and Gorbach, S. L. (1991) Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J. Nutr. 121, 547-555.
5 Mori, T. A. and Beilin, L. J. (2001) Long-chain omega 3 fatty acid blood lipids and cardiovascular risk reduction. Curr. Opin. Lipidol. 12, 11-17.   DOI
6 Mukherjee, A., Wilson, E. M. and Rotwein, P. (2010) Selective signaling by Akt2 promotes bone morphogenetic protein2-mediated osteoblast differentiation. Mol. Cell. Biol. 30, 1018-1027.   DOI
7 Otsuka, E., Notoya, M. and Hagiwara, H. (2003) Treatment of myoblastic C2C12 cells with BMP-2 stimulates vitamin D-induced formation of osteoclasts. Calcif. Tissue Int. 73, 72-77.   DOI
8 Park, C. K., Lee, Y., Chang, E. J., Lee, M. H., Yoon, J. H., Ryu, J. H. and Kim, H. H. (2008) Bavachalcone inhibits osteoclast differentiation through suppression of NFATc1 induction by RANKL. Biochem. Pharmacol. 75, 2175-2182.   DOI
9 Park, Y. R., Eun, J. S., Choi, H. J., Nepal, M., Kim, D. K., Seo, S. Y., Li, R., Moon, W. S., Cho, N. P., Cho, S. D., Bae, T. S., Kim, B. I. and Soh, Y. (2009) Hexane-soluble fraction of the common fig, ficus carica, inhibits osteoclast differentiation in murine bone marrowderived macrophages and RAW 264.7 cells. Korean J. Physiol. Pharmacol. 13, 417-424.   DOI
10 Poulsen, R. C., Firth, E. C., Rigers, C. W., Moughan, P. J. and Kruger, M. C. (2007) Specific effects of gamma-linolenic, eicosapentaenoic, and docosahexaenoic ethyl esters on bone post-ovariectomy in rats. Calcif. Tissue Int. 81, 459-471.   DOI
11 Calder, P. C. and Zurier, R. B. (2001) Poryunsaturated fatty acids and rheumatoid arthritis. Curr. Opin. Clin. Nutr. Metab. Care. 4, 115-121.   DOI
12 Choi, H. J., Park, Y. R., Nepal, M., Choi, B. Y., Cho, N. P., Choi, S. H., Heo, S. R., Kim, H. S., Yang, M. S. and Soh, Y. (2010) Inhibition of osteoclastogenic differentiation by Ikarisoside A in RAW 264.7 cells via JNK and NF-kappaB signaling pathways. Eur. J. Pharmacol. 636, 28-35.   DOI   ScienceOn
13 Hudert, C. A., Weylandt, K. H., Lu, Y., Wang, J., Hong, S., Dignass, A., Serhan, C. N. and Kang J. X. (2006) Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis. Proc. Natl. Acad. Sci. USA. 103, 11276-11281.   DOI
14 Kobayashi, N., Kadono, Y., Naito, A., Matsumoto, K., Yamamoto, T., Tanaka, S. and Inoue, J. (2001) Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis. EMBO J. 20, 1271-1280.   DOI
15 Yoshida, H., Hayashi, S., Kunisada, T., Ogawa, M., Nishikawa, S., Okamura, H., Sudo, T., Shultz, L. D. and Nishikawa, S. (1990) The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature. 345, 442-444.   DOI
16 Lee, S. E., Woo, K. M., Kim, S. Y., Kim, H. M., Kwack, K., Lee, Z. H. and Kim, H. H. (2002) The phosphatidylinositol 3-kinase, p38, and extracellular signal-regulated kinase pathways are involved in osteoclast differentiation. Bone 30, 71-77.
17 Lee, W. T. (1996) Coloured standard illustrations of Korean plants. pp. 642. Academy Press, Seoul.
18 Liu, C., Walter, T. S., Huang, P., Zhang, S., Zhu, X., Wu, Y., Wedderburn, L. R., Tang, P., Owens, R. J., Stuart, D. I., Ren, J. and Gao, B. (2010) Structural and functional insights of RANKL-RANK interaction and signaling. J. Immunol. 184, 6910-6919.   DOI
19 Theill, L. E., Boyle, W. J. and Penninger, J. M. (2002) RANK-L and RANK: T cells, bone loss, and mammalian evolution. Annu. Rev. Immunol. 20, 795-823.   DOI
20 Yaqoob, P. and Calder, P. (1995) Effects of dietary lipid manipulation upon inflammatory mediator production by murine macrophages. Cell Immunol. 163, 120-128.   DOI
21 Zhao, Q., Shao, J., Chen, W. and Li, Y. P. (2007) Osteoclast differentiation and gene regulation. Front Biosci. 12, 2519-2529   DOI
22 Simopoulos, A. P., Kifer, R. R. and Wykes, A. A. (1991) Omega 3 fatty acid: Research advance and support in the fi eld since June 1985(worldwide). World Rev Nutr Diet. 66, 51-71.
23 Raggatt, L. J. and Partridge, N. C. (2010) Cellular and molecular mechanisms of bone remodeling. J. Biol. Chem. 285(33), 25103-25108.   DOI
24 Rahman, M. M., Bhattacharya, A. and Fernandes, G. (2008) Docosahexaenoic acid is more potent inhibitor of osteoclast differentiation in RAW 264.7 cells than eicosapentaenoic acid. J. Cell. Physiol. 214, 201-209   DOI
25 Reddy, S. V., Hundley, J. E., Windle, J. J., Alcantara, O., Linn, R., Leach, R. J., Boldt, D. H. and Roodman, G. D. (1995) Characterization of the mouse tartrate-resistant acid phosphatase (TRAP) gene promoter. J. Bone Miner. Res. 10, 601-606.
26 Sun, D., Krishnan, A., Zaman K., Lawrence, R., Bhattacharya, A. and Fernandes, G. (2003) Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomizes mice. J. Bone Miner Res. 18, 1206-1216.   DOI
27 Tachi, K., Takami, M., Sato, H., Mochizuki, A., Zhao, B., Miyamoto, Y., Tsukasaki, H., Inoue, T., Shintani, S., Koike, T., Honda, Y., Suzuki, O., Baba, K. and Kamijo, R. (2010a) Enhancement of bone morphogenetic protein-2-inhanced ectopic bone formation by transforming growth $factor-{\beta}1$. Tissue Eng. Part A. Epub ahead of print.