Browse > Article
http://dx.doi.org/10.3746/jkfn.2015.44.4.532

Effect of Spinach Extract on RANKL-Mediated Osteoclast Differentiation  

Kim, Dong-Gyu (Namhae Garlic Research Institute)
Kim, Mi-Hye (Namhae Garlic Research Institute)
Kang, Min Jung (Namhae Garlic Research Institute)
Shin, Jung Hye (Namhae Garlic Research Institute)
Publication Information
Journal of the Korean Society of Food Science and Nutrition / v.44, no.4, 2015 , pp. 532-539 More about this Journal
Abstract
Inhibition of osteoclast differentiation is the most important target for prevention of inflammatory bone resorption and bone diseases. Here, we investigated the effect of spinach ethanol extract on osteoclast differentiation in RAW264.7 cells. Spinach was extracted with ethanol at a concentration ranging from 0 to 100% (0, 25, 50, 75, and 100% ethanol). Inhibitory effects of receptor activator of NF-${\kappa}B$ ligan (RANKL)-induced osteoclast differentiation were evaluated using tartrate-resistant acid phosphatase (TRAP) stain assay. The most effective eanol concentration for osteoclast differentiation was 100%. Spinach extract (100% ethanol) suppressed RANKL-induced osteoclast differentiation and TRAP activity. Spinach extract (100% ethanol) also suppressed expression of osteoclast differentiation-related marker genes (NFATc1, c-FOS, cathepsin K, and TRAP) and down-regulated RANKL-induced NF-${\kappa}B$ and ERK phosphorylation during osteoclast differentiation. Taken together, our results suggest that spinach extract is effective against reducing osteoclast differentiation through the NF-${\kappa}B$-mediated pathway.
Keywords
spinach; osteoclast; tartrate-resistant acid phosphatase (TRAP); RANKL; c-Fos;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Titorencu I, Pruna V, Jinga VV, Simionescu M. 2014. Osteoblast ontogeny and implications for bone pathology: an overview. Cell Tissue Res 355: 23-33.   DOI
2 Rodan GA, Martin TJ. 2000. Therapeutic approaches to bone diseases. Science 289: 1508-1514.   DOI
3 Walsh MC, Kim N, Kadono Y, Rho J, Lee SY, Lorenzo J, Choi Y. 2006. Osteoimmunology: interplay between the immune system and bone metabolism. Annu Rev Immunol 24: 33-63.   DOI
4 Wang C, Wang X, Xu XL, Yuan XL, Gou WL, Wang AY, Guo QY, Peng J, Lu SB. 2014. Bone microstructure and regional distribution of osteoblast and osteoclast activity in the osteonecrotic femoral head. PLoS ONE 9: e96361.   DOI
5 Beederman M, Farina EM, Reid RR. 2014. Molecular basis of cranial suture biology and disease: Osteoblastic and osteoclastic perspectives. Genes Dis 1: 120-125.   DOI
6 Tsubaki M, Komai M, Itoh T, Imano M, Sakamoto K, Shimaoka H, Takeda T, Ogawa N, Mashimo K, Fujiwara D, Mukai J, Sakaguchi K, Satou T, Nishida S. 2014. Nitrogen-containing bisphosphonates inhibit RANKL- and MCSF-induced osteoclast formation through the inhibition of ERK1/2 and Akt activation. J Biomed Sci 21: 10.   DOI
7 Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. 1998. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93: 165-176.   DOI
8 Soysa NS, Alles N, Shimokawa H, Jimi E, Aoki K, Ohya K. 2009. Inhibition of the classical NF-kappaB pathway prevents osteoclast bone-resorbing activity. J Bone Miner Metab 27: 131-139.   DOI
9 Takeda S, Yoshizawa T, Nagai Y, Yamato H, Fukumoto S, Sekine K, Kato S, Matsumoto T, Fujita T. 1999. Stimulation of osteoclast formation by 1,25-dihydroxyvitamin D requires its binding to vitamin D receptor (VDR) in osteoblastic cells: studies using VDR knockout mice. Endocrinology 140: 1005-1008.   DOI
10 Miyaura C, Inada M, Matsumoto C, Ohshiba T, Uozumi N, Shimizu T, Ito A. 2003. An essential role of cytosolic phospholipase $A2{\alpha}$ in prostaglandin E2-mediated bone resorption associated with inflammation. J Exp Med 197: 1303-1310.   DOI
11 Wei S, Kitaura H, Zhou P, Ross FP, Teitelbaum SL. 2005. IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest 115: 282-290.   DOI
12 Feng X, McDonald JM. 2011. Disorders of bone remodeling. Annu Rev Pathol 6: 121-145.   DOI
13 Kim HJ, Yoon HJ, Kim SY, Yoon YR. 2014. A mediumchain fatty acid, capric acid, inhibits RANKL-induced osteoclast differentiation via the suppression of NF-${\kappa}B$ signaling and blocks cytoskeletal organization and survival in mature osteoclasts. Mol Cells 37: 598-604.   DOI
14 Li DZ, Zhang QX, Dong XX, Li HD, Ma X. 2014. Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-${\kappa}B$ pathways in murine RAW264.7 cells. J Bone Miner Metab 32: 494-504.   DOI
15 Wagner EF, Eferl R. 2005. Fos/AP-1 proteins in bone and the immune system. Immunol Rev 208: 126-140.   DOI
16 Teitelbaum SL, Ross FP. 2003. Genetic regulation of osteoclast development and function. Nat Rev Genet 4: 638-649.   DOI
17 Kim JH, Kim N. 2014. Regulation of NFATc1 in osteoclast differentiation. J Bone Metab 21: 233-241.   DOI
18 Kavitha CV, Deep G, Gangar SC, Jain AK, Agarwal C, Agarwal R. 2014. Silibinin inhibits prostate cancer cells- and RANKL-induced osteoclastogenesis by targeting NFATc1, NF-${\kappa}B$, and AP-1 activation in RAW264.7 cells. Mol Carcinog 53: 169-180.   DOI
19 Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D, Galibert L. 1997. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendriticcell function. Nature 390: 175-179.   DOI
20 Battaglino R, Kim D, Fu J, Vaage B, Fu XY, Stashenko P. 2002. c-myc is required for osteoclast differentiation. J Bone Miner Res 17: 763-773.   DOI
21 Lee MH, Han JS, Kozukue N, Minamide T. 2005. Physicochemical characteristics of commercial spinach produced in autumn. J East Asian Soc Dietary Life 15: 306-314.
22 Kim NY, Yoon SK, Jang MS. 1993. Effect of blanching on the chemical properties of different kind of spinach. Korean J Soc Food Sci 9: 204-209.
23 Lomnitski L, Bergman M, Nyska A, Ben-Shaul V, Grossman S. 2003. Composition, efficacy, and safety of spinach extracts. Nutr Cancer 46: 222-231.   DOI
24 Bohlooli S, Barmaki S, Khoshkhahesh F, Nakhostin-Roohi B. 2014. The effect of spinach supplementation on exerciseinduced oxidative stress. J Sports Med Phys Fitness [Epub ahead of print].
25 Ko SH, Park JH, Kim SY, Lee SW, Chun SS, Park E. 2014. Antioxidant effects of spinach (Spinacia oleracea L.) supplementation in hyperlipidemic rats. Prev Nutr Food Sci 19: 19-26.   DOI
26 Seo JH, Kang HW, Han JS. 2012. Quality characteristics of Jajang noodles with added spinach. J East Asian Soc Dietary Life 22: 278-289.
27 Moon HJ, Ko WK, Han SW, Kim DS, Hwang YS, Park HK, Kwon IK. 2012. Antioxidants, like coenzyme Q10, selenite, and curcumin, inhibited osteoclast differentiation by suppressing reactive oxygen species generation. Biochem Biophys Res Commun 418: 247-253.   DOI
28 de Kok JB, Roelofs RW, Giesendorf BA, Pennings JL, Waas ET, Feuth T, Swinkels DW, Span PN. 2005. Normalization of gene expression measurements in tumor tissues: comparison of 13 endogenous control genes. Lab Invest 85: 154-159.   DOI
29 Lee JH, Kim HN, Yang D, Jung K, Kim HM, Kim HH, Ha H, Lee ZH. 2009. Trolox prevents osteoclastogenesis by suppressing RANKL expression and signaling. J Biol Chem 284: 13725-13734.   DOI
30 Sriarj W, Aoki K, Ohya K, Takahashi M, Takagi Y, Shimokawa H. 2015. TGF-${\beta}$ in dentin matrix extract induces osteoclastogenesis in vitro. Odontology 103: 9-18.   DOI
31 Liu YQ, Zhan LB, Liu T, Cheng MC, Liu XY, Xiao HB. 2014. Inhibitory effect of Ecliptae herba extract and its component wedelolactone on pre-osteoclastic proliferation and differentiation. J Ethnopharmacol 157: 206-211.   DOI
32 Lee SE, Woo KM, Kim SY, Kim HM, Kwack K, Lee ZH, Kim HH. 2002. The phosphatidylinositol 3-kinase, p38, and extracellular signal-regulated kinase pathways are involved in osteoclast differentiation. Bone 30: 71-77.
33 Chung YH, Choi B, Song DH, Song Y, Kang SW, Yoon SY, Kim SW, Lee HK, Chang EJ. 2014. Interleukin-$1{\beta}$ promotes the LC3-mediated secretory function of osteoclast precursors by stimulating the $Ca^{2+}$-dependent activation of ERK. Int J Biochem Cell Biol 54: 198-207.   DOI