Korean Journal of Medicinal Crop Science (한국약용작물학회지)

The Korean Society of Medicinal Crop Science (한국약용작물학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Oleanolic Acid and its Derivatives on the Differentiation of MC3T3-E1 Osteoblastic Cell

Oleanolic acid 및 그 유도체가 MC3T3-E1 조골세포주의 분화에 미치는 효과

  • Kim, Se-Won (Department of Food and Nutrition, Hanyang University) ;
  • Lee, Chang-Ho (Department of Pharmacology, Hanyang University) ;
  • Jung, Hee-Kung (School of Biomedical Science & Engineering, Hanyang University) ;
  • Jo, Sung-Sin (School of Biomedical Science & Engineering, Hanyang University) ;
  • Lee, Hong-Ki (School of Biomedical Science & Engineering, Hanyang University) ;
  • Park, Yong-Soon (Department of Food and Nutrition, Hanyang University)
  • 김세원 (한양대학교 식품영양학과) ;
  • 이창호 (한양대학교 의과대학 약리학교실) ;
  • 정희경 (한양대학교 의생명공학과) ;
  • 조성신 (한양대학교 의생명공학과) ;
  • 이홍기 (한양대학교 의생명공학과) ;
  • 박용순 (한양대학교 식품영양학과)
  • Received : 2011.11.22
  • Accepted : 2011.12.22
  • Published : 2011.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

Ursolic acid, triterpenoid compound has been shown to stimulate osteoblast differentiation and enhance bone formation. In the present study, we examined the effects of similar triterpenoid compounds, oleanolic acid (OA) and its derivatives, such as oleanolic acid acetate (OAA) and oleanolic acetate methyl ester (OAM) on the bone formation in MC3T3-E1 osteoblast cells. We determined cellular proliferation, alkaline phosphatase (ALP) activity, mineralization, and expression of osteoblast specific genes and mitogen activated protein kinase phosphorylation. Treatment of $0.1-10{\mu}m$ OA, OAA, and OAM increased cellular proliferation, but not significantly increased as compared with dimethyl sulfoxide (DMSO). OA, OAA, and OAM at 5uM concentration enhanced ALP expression, mineralization, and osteocalcin (OCN) mRNA level. In conclusion, OA and its derivatives stimulated the osteoblast differentiation by increasing ALP, mineralization, and OCN mRNA expression. However, there were no significantly difference on osteoblast differentiation among treatment of OA, OAA, and OAM.

Keywords

References

  1. Anderson JJ and Garner SC. (1998). Phytoestrogen and bone. Bailliere's Clinical Endocrinology and Metabolism. 12:543-557. https://doi.org/10.1016/S0950-351X(98)80003-7
  2. Bachhav SS, Patil SD, Bhutada MS and Surana SJ. (2011). Oleanolic acid prevents glucocorticoid-induced hypertension in rats. Phytotherapy Research. 25:1435-1439. https://doi.org/10.1002/ptr.3431
  3. Byers BA and García AJ. (2004). Exogenous Runx2 expression enhances in vitro osteoblastic differentiation and mineralization in primary bone marrow stromal cells. Tissue Engineering. 10:1623-1632. https://doi.org/10.1089/ten.2004.10.1623
  4. Boonen A, Broos P and Deqeker J. (1997). The prevention of treatment of age related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF-I or rhRGF-$\beta$w): a perspective. Journal of Internal Medicine. 242:285-290. https://doi.org/10.1046/j.1365-2796.1997.00133.x
  5. Bradford MM. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry. 72:248-254. https://doi.org/10.1016/0003-2697(76)90527-3
  6. Byers BA and García AJ. (2004). Exogenous Runx2 expression enhances in vitro osteoblastic differentiation and mineralization in primary bone marrow stromal cells. Tissue Engineering. 10:1623-32. https://doi.org/10.1089/ten.2004.10.1623
  7. Christian JC, Yu PL, Slemenda CW and Johnston CC Jr. (1989). Heritability of bone mass: a longitudinal study in aging male twins. The American Journal of Human Genetics. 44:429-433.
  8. Cheng SL, Shin CS, Towler DA and Civitelli R. (2000). A dominant negative cadherin inhibits osteoblast differentiation. Journal of Bone and Mineral Research. 15:2362-2370. https://doi.org/10.1359/jbmr.2000.15.12.2362
  9. Cheung WM, Ng WW and Kung AW. (2006). Dimethyl sulfoxide as an inducer of differentiation in preosteoblast MC3T3-E1 cells. FEBS Letters. 580:121-126. https://doi.org/10.1016/j.febslet.2005.11.062
  10. Cho SH, Kim KG, Kim SR, Lee jA, Moom H and Hwang YY. (1996). The effects of 17-$\beta$ estradiol, medroxyprogesterone acetate and parathyroid hormone on the differentiation of osteoblast cell. Korean Journal of Obstetrics & Gynecology. 39:1497-1506.
  11. Delmas PD. (2002). Treatment of postmenopausal osteoporosis. Lancet 359:2018-2026. https://doi.org/10.1016/S0140-6736(02)08827-X
  12. Dinkova-Kostova AT, Liby KT, Stephenson KK, Holtzclaw WD, Gao X, Suh N, Williams C, Risingsong R, Honda T, Gribble GW, Sporn MB and Talalay P. (2005). Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress. Proceedings of the National Academy of Sciences of the United States of America. 12:4584-4589.
  13. Ebeling PR, Atley LM and Guthrie JR. (1996). Bone turnover markers and bone density across the menopausal transition. The Journal of Clinical Endocrinology & Metabolism. 81:3366-3371. https://doi.org/10.1210/jc.81.9.3366
  14. Hauschka PV, Lian JB, Cole DEC and Gundberg CM. (1989). Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiological Reviews. 69: 990-1047.
  15. Hipskind RA and Bilbe G. (1998). MAP kinase signaling cascades and gene expression in osteoblasts. Frontiers in Bioscience. 3: 804-816.
  16. Hanai Y, Tokuda H and Ishisaki A. (2006). The involvement of p44/p42 MAP kinase in insulin-like growth factor-I-induced alkaline phosphatase activity in osteoblast like MC3T3-E1 cells. Molecular and Cellular Endocrinology. 251: 42-48. https://doi.org/10.1016/j.mce.2006.02.014
  17. Ji SH, Ahn DH and Jun M. (2010). Effects of Petasites japonicus and Momordica charantia L. extracts on MC3T3-E1 osteoblastic cells. Journal of Food Science and Nutrition. 39:203-209.
  18. Jie L. (1995). Pharmacology of oleanolic acid and ursolic acid. Journal of Ethnopharmacology. 49:57-68 https://doi.org/10.1016/0378-8741(95)90032-2
  19. Jeong JG, Kim YS, Min YK and Kim SH. (2008). Low concentration of 3-carene stimulates the differentiation of mouse osteoblastic MC3T3-E1 subclone 4 cells. Phytotherapy Research. 22:18-22. https://doi.org/10.1002/ptr.2247
  20. Jun JH, Ryoo HM, Woo KM, Kim GS and Baek JH. (2009). Bone morphogenetic protein 2-induced MAPKs activation is independent of the Smad1/5 activation. International Journal of Oral Biology. 34:115-121.
  21. Kwak HB, Tang D, Ha H, Lee JH, Kim HN, Woo ER and Hee H. (2006). Tanshinone IIA isolated from Salvia miltiorrhiza Bunge inhibits osteoclast differentiation and bone resorption. Korean Journal of Medicinal Crop Science. 14:146-147.
  22. Kwon JW, Lee HK, Park HJ, Kwon TO, Choi HR and Song JY. (2011). Screening of biologocal activities to different ethanol extracts of Rubus coreanus Miq. Korean Journal of Medicinal Crop Science. 19:325-333. https://doi.org/10.7783/KJMCS.2011.19.5.325
  23. Kleerekoper M and Mendlovic DB. (1993). Sodium fluoride therapy of postmenopausal osteoporosis. Endocrine Reviews. 14:312-323.
  24. Kozawa O, Hatakeyama D and Uematsu T. (2002). Divergent regulation by p44/p42 MAP kinase and p38 MAP kinase of bone morphogenetic protein-4-stimulated osteocalcin synthesis in osteoblasts. Journal of Cellular Biochemistry. 84:583-589. https://doi.org/10.1002/jcb.10056
  25. Lee SU, Park SJ, Kwak HB, Oh J, Min YK and Kim SH. (2008). Anabolic activity of ursolic acid in bone: Stimulating osteoblast differentiation in vitro and inducing new bone formation in vivo. Pharmacological Research. 58:290-296 https://doi.org/10.1016/j.phrs.2008.08.008
  26. Lips P. (2001). Vitamin D deficiency and secondary hyperpar athyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocrine Reviews. 22:477-501. https://doi.org/10.1210/er.22.4.477
  27. Liu J, Wu Q, Lu YF and Pi J. (2008). New insights into generalized hepatoprotective effects of oleanolic acid: key roles of metallothionein and Nrf2 induction. Biochemical Pharmacology. 76:922-928. https://doi.org/10.1016/j.bcp.2008.07.021
  28. Maeda T, Matsunuma A, Kawane T and Horiuchi N. (2001). Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells. Biochemical and Biophysical Research Communications. 280:874-877. https://doi.org/10.1006/bbrc.2000.4232
  29. Musabayane CT, Tufts MA and Mapanga RF. (2010). Synergistic antihyperglycemic effects between plant-derived oleanolic acid and insulin in streptozotocin-induced diabetic rats. Renal Failure. 32:832-839. https://doi.org/10.3109/0886022X.2010.494802
  30. Marumo K and Saito M. (2011). Effects of parathyroid hormone (teriparatide) on bone mass and quality in osteoporosis. Japanese Journal of Clinical Medicine. 69:1264-1269.
  31. Owen TA, Aronow M, Shalhoub V, Barone LM, Wilming L and Tassinari MS. (1990). Progressive development of the rat osteoblast phenotype in vitro: Reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix. Journal of Cellular Physiology. 143:420-430. https://doi.org/10.1002/jcp.1041430304
  32. Parfitt AM. (1994). Osteonal and hemi-osteonal remodeling: The spatial and temporal framework for signal traffic in adult human bone. Journal of Cellular Biochemistry. 55:273-286. https://doi.org/10.1002/jcb.240550303
  33. Park HP, Lee JW, Kim HJ and Lee IS. (2005). Effects of Solidago uirga-aurea var. gigantea Miq. root extracts on the activity and differentiation of MC3T3-E1 osteoblastic cell. Journal of Food Science and Nutrition. 34:929-936.
  34. Pittenger JJ, Mackay AM, Beck SC, Jaiswal RK, Douglas R and Mosca JD. (1999). Multilineage potential of adult human mesenchymal stem cells. Science. 284:143-147. https://doi.org/10.1126/science.284.5411.143
  35. Sudo H, Kodama H, Amagai Y, Yamamoto S and Kasai S. (1983). In vitro differentiation and calcification in new clonal osteogenic cell line derived from newbone mouse calvaria. The Journal of Cell Biology. 96:191-198. https://doi.org/10.1083/jcb.96.1.191
  36. Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT and Martin TJ. (1999). Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocrine Reviews. 20:345-357. https://doi.org/10.1210/er.20.3.345
  37. Zhou R, Zhang Z, Zhao L, Jia C, Xu S, Mai Q, Lu M, Huang M, Wang L, Wang X, Jin D and Bai X. (2011). Inhibition of mTOR signaling by oleanolic acid contributes to its anti-tumor activity in osteosarcoma cells. Journal of Orthopaedic Research. 29:846-852. https://doi.org/10.1002/jor.21311
  38. Zhang Y, Li JX, Zhao J, Wang SZ, Pan Y, Tanaka K and Kadota S. (2005). Synthesis and activity of oleanolic acid derivatives, a novel class of inhibitors of osteoclast formation. Bioorganic & Medicinal Chemistry Letters. 15:1629-1632. https://doi.org/10.1016/j.bmcl.2005.01.061

Cited by

  1. Isolation and Identification of Antioxidant Compound from the Lythrum Salicaria L. Roots vol.57, pp.4, 2014, https://doi.org/10.3839/jabc.2014.057
  2. Spica Prunella extract inhibits phosphorylation of JNK, ERK and IκBα signals during osteoclastogenesis vol.22, pp.6, 2013, https://doi.org/10.1007/s10068-013-0268-5