Icaritin, an Exogenous Phytomolecule, Enhances Osteogenesis but Not Angiogenesis-An In Vitro Efficacy Study

PLoS ONE

Volumn 7, Issue 8, 2012, Pages

  Yao, Dong ^a   Xie, Xin Hui ^a,b   Wang, Xin Luan ^a,c   Wan, Chao ^d,e   Lee, Wayne Y W ^a   Chen, Shi Hui ^a   Pei, Duan Qing ^f   Wang, Yi Xiang ^a   Li, Gang ^a   Qin, Ling ^a,c  

^a CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^b THE FIRST AFFILIATED HOSPITAL OF SOOCHOW UNIVERSITY   (China)

^c SHENZHEN INSTITUTES OF ADVANCED TECHNOLOGY   (China)

^d Prince of Wales Hospital   (Hong Kong)

^e BEIJING UNIVERSITY OF POSTS AND TELECOMMUNICATIONS   (China)

^f GUANGZHOU INSTITUTES OF BIOMEDICINE AND HEALTH   (China)

Author keywords

[No Author keywords available]

Indexed keywords

FLAVONOID; ICARITIN; UNCLASSIFIED DRUG;

ADIPOGENESIS; ANGIOGENESIS; ARTICLE; BONE DEVELOPMENT; CELL DIFFERENTIATION; CELL MIGRATION; CELL PROLIFERATION; CONTROLLED STUDY; DRUG EFFECT; DRUG EFFICACY; FETUS; HUMAN; HUMAN CELL; IN VITRO STUDY; MESENCHYMAL STEM CELL; OSSIFICATION; OSTEOBLAST; UMBILICAL VEIN ENDOTHELIAL CELL;

EPIMEDIUM;

EID: 84865589476     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0041264     Document Type: Article

References (63)

1. Otto WR, Rao J, (2004) Tomorrow's skeleton staff: mesenchymal stem cells and the repair of bone and cartilage. Cell Prolif 37: 97-110.
2. Li WJ, Tuli R, Huang X, Laquerriere P, Tuan RS, (2005) Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold. Biomaterials 26: 5158-5166.
3. Grasser WA, Orlic I, Borovecki F, Riccardi KA, Simic P, et al. (2007) BMP-6 exerts its osteoinductive effect through activation of IGF-I and EGF pathways. Int Orthop 31: 759-765.
4. Kubler NR, Wurzler K, Reuther JF, Faller G, Sieber E, et al. (1999) [EHBMP-2. Initial BMP analog with osteoinductive properties]. Mund Kiefer Gesichtschir 3 Suppl 1: S134-139.
5. Margolin MD, Cogan AG, Taylor M, Buck D, McAllister TN, et al. (1998) Maxillary sinus augmentation in the non-human primate: a comparative radiographic and histologic study between recombinant human osteogenic protein-1 and natural bone mineral. J Periodontol 69: 911-919.
6. Albrektsson T, Johansson C, (2001) Osteoinduction, osteoconduction and osseointegration. Eur Spine J 10 Suppl 2: S96-101.
7. Hidaka S, Okamoto Y, Nakajima K, Suekawa M, Liu SY, (1997) Preventive effects of traditional Chinese (Kampo) medicines on experimental osteoporosis induced by ovariectomy in rats. Calcif Tissue Int 61: 239-246.
8. Hidaka S, Okamoto Y, Yamada Y, Kon Y, Kimura T, (1999) A Japanese herbal medicine, Chujo-to, has a beneficial effect on osteoporosis in rats. Phytother Res 13: 14-19.
9. Li H, Miyahara T, Tezuka Y, Namba T, Suzuki T, et al. (1999) The effect of kampo formulae on bone resorption in vitro and in vivo. II. Detailed study of berberine. Biol Pharm Bull 22: 391-396.
10. Sakamoto S, Sassa S, Kudo H, Suzuki S, Mitamura T, et al. (2000) Preventive effects of a herbal medicine on bone loss in rats treated with a GnRH agonist. Eur J Endocrinol 143: 139-142.
11. Chen WF, Mok SK, Wang XL, Lai KH, Lai WP, et al. (2011) Total flavonoid fraction of the Herba epimedii extract suppresses urinary calcium excretion and improves bone properties in ovariectomised mice. Br J Nutr 105: 180-189.
12. Xie F, Wu CF, Lai WP, Yang XJ, Cheung PY, et al. (2005) The osteoprotective effect of Herba epimedii (HEP) extract in vivo and in vitro. Evid Based Complement Alternat Med 2: 353-361.
13. Zhang G, Qin L, Hung WY, Shi YY, Leung PC, et al. (2006) Flavonoids derived from herbal Epimedium Brevicornum Maxim prevent OVX-induced osteoporosis in rats independent of its enhancement in intestinal calcium absorption. Bone 38: 818-825.
14. Brandi ML, Collin-Osdoby P, (2006) Vascular biology and the skeleton. J Bone Miner Res 21: 183-192.
15. Qin L, Zhang G, Hung WY, Shi Y, Leung K, et al. (2005) Phytoestrogen-rich herb formula "XLGB" prevents OVX-induced deterioration of musculoskeletal tissues at the hip in old rats. J Bone Miner Metab 23 Suppl: 55-61.
16. Ma HP, Ming LG, Ge BF, Zhai YK, Song P, et al. (2010) Icariin is more potent than genistein in promoting osteoblast differentiation and mineralization in vitro. J Cell Biochem.
17. Meng FH, Li YB, Xiong ZL, Jiang ZM, Li FM, (2005) Osteoblastic proliferative activity of Epimedium brevicornum Maxim. Phytomedicine 12: 189-193.
18. Qian G, Zhang X, Lu L, Wu X, Li S, et al. (2006) Regulation of Cbfa1 expression by total flavonoids of Herba epimedii. Endocr J 53: 87-94.
19. Chen KM, Ge BF, Liu XY, Ma PH, Lu MB, et al. (2007) Icariin inhibits the osteoclast formation induced by RANKL and macrophage-colony stimulating factor in mouse bone marrow culture. Pharmazie 62: 388-391.
20. Wang Y, Wan C, Deng L, Liu X, Cao X, et al. (2007) The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest 117: 1616-1626.
21. Wan C, Gilbert SR, Wang Y, Cao X, Shen X, et al. (2008) Activation of the hypoxia-inducible factor-1alpha pathway accelerates bone regeneration. Proc Natl Acad Sci U S A 105: 686-691.
22. Schipani E, Maes C, Carmeliet G, Semenza GL, (2009) Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF. J Bone Miner Res 24: 1347-1353.
23. Barnes GL, Kostenuik PJ, Gerstenfeld LC, Einhorn TA, (1999) Growth factor regulation of fracture repair. J Bone Miner Res 14: 1805-1815.
24. Einhorn TA, (1998) The cell and molecular biology of fracture healing. Clin Orthop Relat Res pp. S7-21.
25. Gerstenfeld LC, Cullinane DM, Barnes GL, Graves DT, Einhorn TA, (2003) Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. J Cell Biochem 88: 873-884.
26. Provot S, Zinyk D, Gunes Y, Kathri R, Le Q, et al. (2007) Hif-1alpha regulates differentiation of limb bud mesenchyme and joint development. J Cell Biol 177: 451-464.
27. Schipani E, Ryan HE, Didrickson S, Kobayashi T, Knight M, et al. (2001) Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival. Genes Dev 15: 2865-2876.
28. Chung BH, Kim JD, Kim CK, Kim JH, Won MH, et al. (2008) Icariin stimulates angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells. Biochem Biophys Res Commun 376: 404-408.
29. Fotsis T, Pepper MS, Aktas E, Breit S, Rasku S, et al. (1997) Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Res 57: 2916-2921.
30. Heim M, Frank O, Kampmann G, Sochocky N, Pennimpede T, et al. (2004) The phytoestrogen genistein enhances osteogenesis and represses adipogenic differentiation of human primary bone marrow stromal cells. Endocrinology 145: 848-859.
31. Sasamura H, Takahashi A, Miyao N, Yanase M, Masumori N, et al. (2002) Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma. Br J Cancer 86: 768-773.
32. Setchell KD, Brown NM, Desai P, Zimmer-Nechemias L, Wolfe BE, et al. (2001) Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. J Nutr 131: 1362S-1375S.
33. Yuan JP, Wang JH, Liu X, (2007) Metabolism of dietary soy isoflavones to equol by human intestinal microflora-implications for health. Mol Nutr Food Res 51: 765-781.
34. Park JS, Park HY, Rho HS, Ahn S, Kim DH, et al. (2008) Statistically designed enzymatic hydrolysis for optimized production of icariside II as a novel melanogenesis inhibitor. J Microbiol Biotechnol 18: 110-117.
35. Zhang G, Qin L, Sheng H, Wang XL, Wang YX, et al. (2009) A novel semisynthesized small molecule icaritin reduces incidence of steroid-associated osteonecrosis with inhibition of both thrombosis and lipid-deposition in a dose-dependent manner. Bone 44: 345-356.
36. Huang J, Yuan L, Wang X, Zhang TL, Wang K, (2007) Icaritin and its glycosides enhance osteoblastic, but suppress osteoclastic, differentiation and activity in vitro. Life Sci 81: 832-840.
37. Chen KM, Ge BF, Ma HP, Liu XY, Bai MH, et al. (2005) Icariin, a flavonoid from the herb Epimedium enhances the osteogenic differentiation of rat primary bone marrow stromal cells. Pharmazie 60: 939-942.
38. Chen KM, Ma HP, Ge BF, Liu XY, Ma LP, et al. (2007) Icariin enhances the osteogenic differentiation of bone marrow stromal cells but has no effects on the differentiation of newborn calvarial osteoblasts of rats. Pharmazie 62: 785-789.
39. Zhao J, Ohba S, Komiyama Y, Shinkai M, Chung UI, et al. (2010) Icariin: a potential osteoinductive compound for bone tissue engineering. Tissue Eng Part A 16: 233-243.
40. Zhao J, Ohba S, Shinkai M, Chung UI, Nagamune T, (2008) Icariin induces osteogenic differentiation in vitro in a BMP- and Runx2-dependent manner. Biochem Biophys Res Commun 369: 444-448.
41. Chamberlain G, Fox J, Ashton B, Middleton J, (2007) Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 25: 2739-2749.
42. Cool SM, Nurcombe V, (2005) The osteoblast-heparan sulfate axis: control of the bone cell lineage. Int J Biochem Cell Biol 37: 1739-1745.
43. Heino TJ, Hentunen TA, Vaananen HK, (2004) Conditioned medium from osteocytes stimulates the proliferation of bone marrow mesenchymal stem cells and their differentiation into osteoblasts. Exp Cell Res 294: 458-468.
44. Schmitt B, Ringe J, Haupl T, Notter M, Manz R, et al. (2003) BMP2 initiates chondrogenic lineage development of adult human mesenchymal stem cells in high-density culture. Differentiation 71: 567-577.
45. Solchaga LA, Penick K, Porter JD, Goldberg VM, Caplan AI, et al. (2005) FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells. J Cell Physiol 203: 398-409.
46. Janderova L, McNeil M, Murrell AN, Mynatt RL, Smith SR, (2003) Human mesenchymal stem cells as an in vitro model for human adipogenesis. Obes Res 11: 65-74.
47. Neubauer M, Fischbach C, Bauer-Kreisel P, Lieb E, Hacker M, et al. (2004) Basic fibroblast growth factor enhances PPARgamma ligand-induced adipogenesis of mesenchymal stem cells. FEBS Lett 577: 277-283.
48. Aubin JE, Liu F, Malaval L, Gupta AK, (1995) Osteoblast and chondroblast differentiation. Bone 17: 77S-83S.
49. Stein GS, Lian JB, Owen TA, (1990) Relationship of cell growth to the regulation of tissue-specific gene expression during osteoblast differentiation. FASEB J 4: 3111-3123.
50. Hirata S, Matsubara T, Saura R, Tateishi H, Hirohata K, (1989) Inhibition of in vitro vascular endothelial cell proliferation and in vivo neovascularization by low-dose methotrexate. Arthritis Rheum 32: 1065-1073.
51. Bocci G, Nicolaou KC, Kerbel RS, (2002) Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs. Cancer Res 62: 6938-6943.
52. Kalghatgi S, Friedman G, Fridman A, Clyne AM, (2010) Endothelial cell proliferation is enhanced by low dose non-thermal plasma through fibroblast growth factor-2 release. Ann Biomed Eng 38: 748-757.
53. Peng Y, Kang Q, Cheng H, Li X, Sun MH, et al. (2003) Transcriptional characterization of bone morphogenetic proteins (BMPs)-mediated osteogenic signaling. J Cell Biochem 90: 1149-1165.
54. Lee MH, Kim YJ, Kim HJ, Park HD, Kang AR, et al. (2003) BMP-2-induced Runx2 expression is mediated by Dlx5, and TGF-beta 1 opposes the BMP-2-induced osteoblast differentiation by suppression of Dlx5 expression. J Biol Chem 278: 34387-34394.
55. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, et al. (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108: 17-29.
56. Nishio Y, Dong Y, Paris M, O'Keefe RJ, Schwarz EM, et al. (2006) Runx2-mediated regulation of the zinc finger Osterix/Sp7 gene. Gene 372: 62-70.
57. Liu HY, Wu AT, Tsai CY, Chou KR, Zeng R, et al. (2011) The balance between adipogenesis and osteogenesis in bone regeneration by platelet-rich plasma for age-related osteoporosis. Biomaterials 32: 6773-6780.
58. Peng S, Zhang G, He Y, Wang X, Leung P, et al. (2009) Epimedium-derived flavonoids promote osteoblastogenesis and suppress adipogenesis in bone marrow stromal cells while exerting an anabolic effect on osteoporotic bone. Bone 45: 534-544.
59. Sheng HH, Zhang GG, Cheung WH, Chan CW, Wang YX, et al. (2007) Elevated adipogenesis of marrow mesenchymal stem cells during early steroid-associated osteonecrosis development. J Orthop Surg Res 2: 15.
60. Kanczler JM, Oreffo RO, (2008) Osteogenesis and angiogenesis: the potential for engineering bone. Eur Cell Mater 15: 100-114.
61. Pepper MS, Ferrara N, Orci L, Montesano R, (1992) Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem Biophys Res Commun 189: 824-831.
62. Cross MJ, Claesson-Welsh L, (2001) FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci 22: 201-207.
63. Xie XH, Wang XL, Zhang G, He YX, Wang XH, et al. (2010) Structural and degradation characteristics of an innovative porous PLGA/TCP scaffold incorporated with bioactive molecular icaritin. Biomed Mater 5 (5): 054109.