Effects of Scytosiphon lomentaria on osteoblastic proliferation and differentiation of MC3T3-E1 cells

  • Park, Mi Hwa (Department of Food and Nutrition, College of Medical and Life Science, Silla University) ;
  • Kim, Seoyeon (Department of Food and Nutrition, College of Medical and Life Science, Silla University) ;
  • Cheon, Jihyeon (Department of Food and Nutrition, College of Medical and Life Science, Silla University) ;
  • Lee, Juyeong (Department of Food and Nutrition, College of Medical and Life Science, Silla University) ;
  • Kim, Bo Kyung (Department of Food and Nutrition, College of Medical and Life Science, Silla University) ;
  • Lee, Sang-Hyeon (Department of Pharmaceutical Engineering, College of Medical and Life Science, Silla University) ;
  • Kong, Changsuk (Department of Food and Nutrition, College of Medical and Life Science, Silla University) ;
  • Kim, Yuck Yong (ISFOOD Co. LTD.) ;
  • Kim, Mihyang (Department of Food and Nutrition, College of Medical and Life Science, Silla University)
  • Received : 2015.09.02
  • Accepted : 2015.12.04
  • Published : 2016.04.01


BACKGROUND/OBJECTIVES: Bone formation and bone resorption continuously occur in bone tissue to prevent the accumulation of old bone, this being called bone remodeling. Osteoblasts especially play a crucial role in bone formation through the differentiation and proliferation. Therefore, in this study, we investigated the effects of Scytosiphon lomentaria extract (SLE) on osteoblastic proliferation and differentiation in MC3T3-E1 cells. MATERIALS/METHODS: A cell proliferation assay, alkaline phosphatase (ALP) activity assay, alizarin red staining and protein expression analysis of osteoblastic genes were carried out to assess the osteoblastic proliferation and differentiation. RESULTS: The results indicated that treatment of SLE promoted the proliferation of MC3T3-E1 cells and improved ALP activity. And, SLE treatment significantly promoted mineralized nodule formation compared with control. In addition, cells treated with SLE significantly upregulated protein expression of ALP, type 1 collagen, bone morphogenetic protein 2, runt-related transcription factor 2, osterix, and osteoprotegerin. CONCLUSIONS: The results demonstrate that SLE promote differentiation inducement and proliferation of osteoblasts and, therefore may help to elucidate the transcriptional mechanism of bone formation and possibly lead to the development of bone-forming drugs.


Supported by : National Research Foundation of Korea


  1. Michaelsson K, Melhus H, Ferm H, Ahlbom A, Pedersen NL. Genetic liability to fractures in the elderly. Arch Intern Med 2005;165:1825-30.
  2. Slemenda CW, Christian JC, Williams CJ, Norton JA, Johnston CC Jr. Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. J Bone Miner Res 1991;6:561-7.
  3. Riggs BL, Khosla S, Melton LJ 3rd. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev 2002;23:279-302.
  4. Isomura H, Fujie K, Shibata K, Inoue N, Iizuka T, Takebe G, Takahashi K, Nishihira J, Izumi H, Sakamoto W. Bone metabolism and oxidative stress in postmenopausal rats with iron overload. Toxicology 2004;197:93-100.
  5. Yonezawa T, Hasegawa S, Asai M, Ninomiya T, Sasaki T, Cha BY, Teruya T, Ozawa H, Yagasaki K, Nagai K, Woo JT. Harmine, a ${\beta}$-carboline alkaloid, inhibits osteoclast differentiation and bone resorption in vitro and in vivo. Eur J Pharmacol 2011;650:511-8.
  6. Lane NE, Kelman A. A review of anabolic therapies for osteoporosis. Arthritis Res Ther 2003;5:214-22.
  7. Yoon HJ, Seo CR, Kim M, Kim YJ, Song NJ, Jang WS, Kim BJ, Lee J, Hong JW, Nho CW, Park KW. Dichloromethane extracts of Sophora japonica L. stimulate osteoblast differentiation in mesenchymal stem cells. Nutr Res 2013;33:1053-62.
  8. Zhang R, Oyajobi BO, Harris SE, Chen D, Tsao C, Deng HW, Zhao M. Wnt/${\beta}$-catenin signaling activates bone morphogenetic protein 2 expression in osteoblasts. Bone 2013;52:145-56.
  9. Demirel Z, Yilmaz-Koz FF, Karabay-Yavasoglu UN, Ozdemir G, Sukatar A. Antimicrobial and antioxidant activity of brown algae from the Aegean sea. J Serb Chem Soc 2009;74:619-28.
  10. Nakamura T, Nagayama K, Kawaguchi S. High tocopherol content in a brown alga Ishige okamurae. Fish Sci 1994;60:793-4.
  11. Hill PA, Tumber A, Meikle MC. Multiple extracellular signals promote osteoblast survival and apoptosis. Endocrinology 1997;138:3849-58.
  12. Tietz NW, Burtis CA, Duncan P, Ervin K, Petitclerc CJ, Rinker AD, Shuey D, Zygowicz ER. A reference method for measurement of alkaline phosphatase activity in human serum. Clin Chem 1983;29:751-61.
  13. Whyte MP. Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization. Endocr Rev 1994;15:439-61.
  14. Niu YB, Li YH, Kong XH, Zhang R, Sun Y, Li Q, Li C, Liu L, Wang J, Mei QB. The beneficial effect of Radix Dipsaci total saponins on one metabolism in vitro and in vivo and the possible mechanisms of action. Osteoporos Int 2012;23:2649-60.
  15. Musial K, Fornalczyk K, Zwolinska D. [Osteopontin (OPN), PDGF-BB(platelet-derived growth factor) and BMP-7 (bone morphogenetic protein) as markers of atherogenesis in children with chronic kidney disease (CKD) treated conservatively--preliminary results]. Pol Merkuriusz Lek 2008;24 Suppl 4:25-7.
  16. W W. Glial line-derived neurotrophic factor (GDNF): biological activities. Folia Morphol (Warsz) 1999;58:155-9.
  17. Li F, Yang Y, Zhu P, Chen W, Qi D, Shi X, Zhang C, Yang Z, Li P. Echinacoside promotes bone regeneration by increasing OPG/RANKL ratio in MC3T3-E1 cells. Fitoterapia 2012;83:1443-50.
  18. Lee HS, Jung EY, Bae SH, Kwon KH, Kim JM, Suh HJ. Stimulation of osteoblastic differentiation and mineralization in MC3T3-E1 cells by yeast hydrolysate. Phytother Res 2011;25:716-23.
  19. Christiansen C. Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 1993;94:646-50.
  20. Rodan GA, Martin TJ. Therapeutic approaches to bone diseases. Science 2000;289:1508-14.
  21. Ducy P, Schinke T, Karsenty G. The osteoblast: a sophisticated fibroblast under central surveillance. Science 2000;289:1501-4.
  22. Hsieh TP, Sheu SY, Sun JS, Chen MH, Liu MH. Icariin isolated from Epimedium pubescens regulates osteoblasts anabolism through BMP-2, SMAD4, and Cbfa1 expression. Phytomedicine 2010;17:414-23.
  23. Chandini SK, Ganesan P, Bhaskar N. In vitro antioxidant activities of three selected brown seaweeds of India. Food Chem 2008;107:707-13.
  24. Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM, Luo SQ. Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappaB. Biochem Biophys Res Commun 2004;314:197-207.
  25. Neve A, Corrado A, Cantatore FP. Osteoblast physiology in normal and pathological conditions. Cell Tissue Res 2011;343:289-302.
  26. Bellows CG, Aubin JE, Heersche JN. Initiation and progression of mineralization of bone nodules formed in vitro: the role of alkaline phosphatase and organic phosphate. Bone Miner 1991;14:27-40.
  27. Horiguchi Y, Nakai T, Kume K. Effects of Bordetella bronchiseptica dermonecrotic toxin on the structure and function of osteoblastic clone MC3T3-E1 cells. Infect Immun 1991;59:1112-6.
  28. Kuhn MC, Willenberg HS, Schott M, Papewalis C, Stumpf U, Flohe S, Scherbaum WA, Schinner S. Adipocyte-secreted factors increase osteoblast proliferation and the OPG/RANKL ratio to influence osteoclast formation. Mol Cell Endocrinol 2012;349:180-8.
  29. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997;89:309-19.
  30. Park KH, Kang JW, Lee EM, Kim JS, Rhee YH, Kim M, Jeong SJ, Park YG, Kim SH. Melatonin promotes osteoblastic differentiation through the BMP/ERK/Wnt signaling pathways. J Pineal Res 2011;51:187-94.
  31. Huang W, Rudkin GH, Carlsen B, Ishida K, Ghasri P, Anvar B, Yamaguchi DT, Miller TA. Overexpression of BMP-2 modulates morphology, growth, and gene expression in osteoblastic cells. Exp Cell Res 2002;274:226-34.
  32. Phimphilai M, Zhao Z, Boules H, Roca H, Franceschi RT. BMP signaling is required for RUNX2-dependent induction of the osteoblast phenotype. J Bone Miner Res 2006;21:637-46.
  33. Liu ZP, Li WX, Yu B, Huang J, Sun J, Huo JS, Liu CX. Effects of trans-resveratrol from Polygonum cuspidatum on bone loss using the ovariectomized rat model. J Med Food 2005;8:14-9.
  34. Rassi CM, Lieberherr M, Chaumaz G, Pointillart A, Cournot G. Down-regulation of osteoclast differentiation by daidzein via caspase 3. J Bone Miner Res 2002;17:630-8.
  35. O'Gorman DM, Tierney CM, Brennan O, O'Brien FJ. The marinederived, multi-mineral formula, Aquamin, enhances mineralisation of osteoblast cells in vitro. Phytother Res 2012;26:375-80.

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