International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Luteolin Induces the Differentiation of Osteoblasts

  • Ko, Seon-Yle (Department of Oral Biochemistry, School of Dentistry, Dankook University)
  • Received : 2010.08.26
  • Accepted : 2010.09.17
  • Published : 2010.09.30
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Abstract

Luteolin is a flavonoid that exists in a glycosylated form in celery and green pepper. Flavonoids possess antioxidant and anti-inflammatory properties and can reduce the expression of key inflammatory molecules in macrophages and monocytes. It has been reported also that some flavonoids have effects on bone metabolism. The effects of luteolin on the function of osteoblasts were investigated by measuring cell viability, alkaline phosphatase activity, type I collagen production, osteoprotegerin secretion, Wnt promoter activity, BMP-2 and Runx2 expression and calcified nodule formation. Luteolin has no effects upon osteoblast viability but induced an increase in alkaline phosphatase activity, type I collagen production and a decrease in osteoprotegerin secretion in these cells. Luteolin treatment also upregulated BMP-2 mRNA expression. These results suggest that luteolin may be a regulatory molecule that facilitates the differentiation of osteoblasts.

Keywords

References

  1. Avila MA, Velasco JA, Cansado J, Notario V. Quercetin mediates the down-regulation of mutant p53 in the human breast cancer cell line MDA-MB468. Cancer Res. 1994; 54:2424-8.
  2. Bellows CG, Aubin JE, Heersche JNM. Initiation and progression of mineralization of bone nodules formed in vitro - the role of alkaline phosphatase and organic phosphate. Bone and Mineral 1991;14:27-40. https://doi.org/10.1016/0169-6009(91)90100-E
  3. Berg C, Neumeyer K, Kirkpatrick P. Teriparatide. Nat Rev Drug Discov. 2003;2:257-8. https://doi.org/10.1038/nrd1068
  4. Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP. High bone density due to a mutation in LDL-receptor-related protein-5. N Engl J Med. 2002;346:1513-21. https://doi.org/10.1056/NEJMoa013444
  5. Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins Growth Factors. 2004;22:233-41. https://doi.org/10.1080/08977190412331279890
  6. Choi EM. Apigenin increases osteoblastic differentiation and inhibits tumor necrosis factor-alpha-induced production of interleukin-6 and nitric oxide in osteoblastic MC3T3-E1 cells. Pharmazie 2007a;62:216-20.
  7. Choi EM. Modulatory effects of luteolin on osteoblastic function and inflammatory mediators in osteoblastic MC3T3- E1 cells. Cell Biology International 2007b;31:870-7. https://doi.org/10.1016/j.cellbi.2007.01.038
  8. Ducy P, Schinke T, Karsenty G. The osteoblast: A sophisticated fibroblast under central surveillance. Science. 2000; 289:1501-4. https://doi.org/10.1126/science.289.5484.1501
  9. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/ Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997;89:747-54. https://doi.org/10.1016/S0092-8674(00)80257-3
  10. Fauran-Clavel MJ, Oustrin J. Alkaline phosphatase and bone calcium parameters. Bone. 1986;7:95-9. https://doi.org/10.1016/8756-3282(86)90680-0
  11. Formica JV, Regelson W. Review of the biology of Quercetin and related bioflavonoids. Food Chem Toxicol. 1995; 33:1061-80. https://doi.org/10.1016/0278-6915(95)00077-1
  12. Fotsis T, Pepper MS, Aktas E, Breit S, Rasku S, Adlercreutz H, Wahala K, Montesano R, Schweigerer L. Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Res. 1997;57:2916-21.
  13. Gao YH, Shinki T, Yuasa T, Kataoka-Enomoto H, Komori T, Suda T, Yamaguchi A. Potential role of cbfa1, an essential transcriptional factor for osteoblast differentiation, in osteoclastogenesis: regulation of mRNA expression of osteoclast differentiation factor (ODF). Biochem Biophys Res Commun. 1998;252:697-702. https://doi.org/10.1006/bbrc.1998.9643
  14. Han LM, Liu B, Xu P. Influence of Herba epimedii flavones on proliferation of osteoblast. Shanghai J tradit Chinese Med. 2003;37:56-8.
  15. Hidaka S, Okamoto Y, Nakajima K. Preventive effects of traditional Chinese medicines on experimental osteoporosis induced by ovariectomy in rats. Caicif Tissue Int. 1997; 61:239-46. https://doi.org/10.1007/s002239900329
  16. Hsu YL, Chang JK, Tsai CH, Chien TT, Kuo PL. Myricetin induces human osteoblast differentiation through bone morphogenetic protein-2/p38 mitogen-activated protein kinase pathway. Biochem Pharmacol. 2007;73:504-14. https://doi.org/10.1016/j.bcp.2006.10.020
  17. Husain SR, Cillard J, Cillard P. Hydroxyl radical scavenging activity of flavonoids. Phytochemistry. 1987;26;2489-92. https://doi.org/10.1016/S0031-9422(00)83860-1
  18. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997;89:755-64. https://doi.org/10.1016/S0092-8674(00)80258-5
  19. Kostenuik PJ, Shalhoub V. Osteoprotegerin: A physiological and pharmacological inhibitor of bone resorption. Curr Pharm Des. 2001;7:613-35. https://doi.org/10.2174/1381612013397807
  20. Lane NE, Kelman A. A review of anabolic therapies for osteoporosis. Arthritis Res Ther. 2003;5:214-22. https://doi.org/10.1186/ar797
  21. Lee KH, Choi EM. Biochanin A stimulates osteoblastic differentiation and inhibits hydrogen peroxide-induced production of inflammatory mediators in MC3T3-E1 cells. Biol Pharm Bull. 2005;28:1948-53. https://doi.org/10.1248/bpb.28.1948
  22. Liu HC, Chen RM, Jian WC, Lin YL. Cytotoxic and antioxidant effects of the water extract of the traditional Chinese herb gusuibu (Drynaria fortunei) on rat osteoblasts. J Formos Med Assoc. 2001;100:383-8.
  23. Lo YC, Chang YH, Wei BL, Huang YL, Chiou WF. Betulinic acid stimulates the differentiation and mineralization of osteoblastic MC3T3-E1 cells: involvement of BMP/Runx2 and beta-catenin signals. J Agric Food Chem. 2010;58:6643-9. https://doi.org/10.1021/jf904158k
  24. Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med. 1995;332:305-11. https://doi.org/10.1056/NEJM199502023320506
  25. Martin JH, Matthews JL. Mitochondrial granules in chondrocytes, osteoblasts and osteocytes. An ultrastructural and microincineration study. Clin Orthop. 1970;68:273-8.
  26. Meng FH, Li YB, Xiong ZL, Jiang ZM, Li FM. Osteoblastic proliferative activity of Epimedium brevicornum Maxim. Phytomedicine. 2005;12:189-93. https://doi.org/10.1016/j.phymed.2004.03.007
  27. Morris C, Thorpe J, Ambrosio L, Santin M. The soybean isoflavone genistein induces differentiation of MG63 human osteosarcoma osteoblasts. J Nutr. 2006;136:1166-70. https://doi.org/10.1093/jn/136.5.1166
  28. Notoya M, Tsukamoto Y, Nishimura H, Woo JT, Nagai K, Lee IS, Hagiwara H. Quercetin, a flavonoid, inhibits the proliferation, differentiation, and mineralization of osteoblasts in vitro. Eur J Pharmacol. 2004;485:89-96. https://doi.org/10.1016/j.ejphar.2003.11.058
  29. Owen ME. Lineage of osteogenic cells and their relationship to the stromal system. in Bone and Mineral Research, edited by Peck WA, pp 1-25, Elsevier Science Publisher, Amsterdam, 1985.
  30. Prouillet C, Mazière JC, Mazière C, Wattel A, Brazier M, Kamel S. Stimulatory effect of naturally occurring flavonols quercetin and kaempferol on alkaline phosphatase activity in MG-63 human osteoblasts through ERK and estrogen receptor pathway. Biochem Pharmacol. 2004;67:1307-13. https://doi.org/10.1016/j.bcp.2003.11.009
  31. Rodan GA, Martin TJ. Therapeutic approaches to bone diseases. Science. 2000;289:1508-14. https://doi.org/10.1126/science.289.5484.1508
  32. Stein GS, Lian JB. Molecular mechanisms mediating proliferation/ differentiation interrelationships during progressive development of the osteoblast phenotype. Endocr Rev. 1993;14:424-42. https://doi.org/10.1210/edrv-14-4-424
  33. Sugimoto E, Yamaguchi M. Anabolic effect of genistein in osteoblastic MC3T3-E1 cells. Int J Mol Med. 2000;5:515-20.
  34. Suzuki H, Hayakawa M, Kobayashi K, Takiguchi H, Abiko Y. H2O2-derived free radicals treated fibronectin substratum reduces the bone nodule formation of rat calvarial osteoblast. Mech Ageing Dev. 1997;98:113-25. https://doi.org/10.1016/S0047-6374(97)00077-8
  35. Wang X, Goh CH, Li B. p38 mitogen-activated protein kinase regulates osteoblast differentiation through osterix. Endocrinology. 2007;148:1629-37. https://doi.org/10.1210/en.2006-1000
  36. Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA. Novel regulators of bone formation: molecular clones and activities. Science. 1988;242:1528-34. https://doi.org/10.1126/science.3201241
  37. Xie F, Wu CF, Lai WP, Yang XJ, Cheung PY, Yao XS, Leung PC, Wong MS. The osteoprotective effect of Herba epimedii (HEP) extract in vivo and in vitro. eCAM. 2005;2:353-61.
  38. Yin XX, Chen ZQ, Liu ZJ, Ma QJ, Dang GT. Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein-2. Chin Med J (Engl). 2007;120:204-10.
  39. Yoshida H, Teramoto T, Ikeda K, Yamori Y. Glycitein effect on suppressing the proliferation and stimulating the differentiation of osteoblastic MC3T3-E1 cells. Biosci Biotechnol Biochem. 2001;65:1211-3. https://doi.org/10.1271/bbb.65.1211
  40. Zhang DW, Cheng Y, Wang NL, Zhang JC, Yang MS, Yao XS. Effects of total flavonoids and flavonol glycosides from Epimedium koreanum Nakai on the proliferation and differentiation of primary osteoblasts. Phytomedicine. 2008; 15:55-61. https://doi.org/10.1016/j.phymed.2007.04.002
  41. Zhang Y, Zeng X, Zhang L, Zheng X. Stimulatory effects of puerarin on bone formation through activation of PI3K/Akt pathway in rat calvaria osteoblasts. Planta Med. 2007; 73:341-7. https://doi.org/10.1055/s-2007-967168