Natural products for treatment of osteoporosis: The effects and mechanisms on promoting osteoblast-mediated bone formation

Life Sciences

Volumn 147, Issue , 2016, Pages 46-58

  An, Jing ^a   Yang, Hao ^a   Zhang, Qian ^a   Liu, Cuicui ^a   Zhao, Jingjing ^a   Zhang, Lingling ^a   Chen, Bo ^a  

^a XI'AN JIAOTONG UNIVERSITY   (China)

Author keywords

Molecular mechanism; Natural products; Osteoblasts; Osteoporosis; Traditional Chinese medicines

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 2 MORPHOLINO 8 PHENYLCHROMONE; 4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; 4 CARBOXYGLUTAMIC ACID; AGENTS AFFECTING METABOLISM; ALKALINE PHOSPHATASE; ANTHRA[1,9 CD]PYRAZOL 6(2H) ONE; AURANTIIN; BERGAPTEN; BONE SIALOPROTEIN; CCAAT ENHANCER BINDING PROTEIN BETA; COLLAGEN TYPE 1; COSTUNOLIDE; ICARIIN; KOBOPHENOL A; NATURAL PRODUCT; OSTEOCALCIN; OSTEOPONTIN; PENTOSALEN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; QUERCETIN; QUERCITRIN; RUTOSIDE; SALIDROSIDE; SALVIANOLIC ACID B; SWEROSIDE; TAXIFOLIN; TRANSCRIPTION FACTOR OSTERIX; TRANSCRIPTION FACTOR RUNX2; UNCLASSIFIED DRUG; BIOLOGICAL PRODUCT;

ADIPOGENESIS; ARTICLE; BONE MATRIX; BONE METABOLISM; BONE MINERALIZATION; BONE REMODELING; CELL DIFFERENTIATION; CELL PROLIFERATION; CHINESE MEDICINE; MESENCHYMAL STEM CELL; OSSIFICATION; OSTEOBLAST; OSTEOLYSIS; OSTEOPOROSIS; OXIDATIVE STRESS; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TRANSACTIVATION; ANIMAL; BONE DEVELOPMENT; DRUG EFFECTS; HUMAN; METABOLISM; PATHOPHYSIOLOGY;

ANIMALS; BIOLOGICAL PRODUCTS; CELL DIFFERENTIATION; CELL PROLIFERATION; HUMANS; MEDICINE, CHINESE TRADITIONAL; OSTEOBLASTS; OSTEOGENESIS; OSTEOPOROSIS;

EID: 84956798627     PISSN: 00243205     EISSN: 18790631     Source Type: Journal    
DOI: 10.1016/j.lfs.2016.01.024     Document Type: Review

References (125)

1. G. Karsenty The complexities of skeletal biology Nature 423 2003 316 318
2. M.R. Urist Bone: formation by autoinduction Science 150 1965 893 899
3. D.J. Hadjidakis, and I. Androulakis Bone remodeling Ann. N. Y. Acad. Sci. 1092 2006 385 396
4. L.G. Raisz Pathogenesis of osteoporosis: concepts, conflicts, and prospects J. Clin. Investig. 115 2005 3318 3325
5. B.L. Riggs, H. Wahner, E. Seeman, K. Offord, W. Dunn, R. Mazess, and et al. Changes in bone mineral density of the proximal femur and spine with aging J. Clin. Investig. 70 1982 716 723
6. A. Leboime, C. Confavreux, N. Mehsen, J. Paccou, C. David, and C. Roux Osteoporosis and mortality Joint Bone Spine 77 Suppl. 2 2010 S107 S112
7. M.C.A. Buencamino, A.L. Sikon, A. Jain, and H.L. Thacker An observational study on the adherence to treatment guidelines of osteopenia J. Women's Health 18 2009 873 881
8. O. Johnell, and J.A. Kanis An estimate of the worldwide prevalence and disability associated with osteoporotic fractures Osteoporos. Int. 17 2006 1726 1733
9. C. Hu, C. Wang, L. Mo, C. Lin, and L. Sun A review on antiosteoporotic drugs Chin. J. Gerontol. 11 2008 2178 2180
10. P. Piscitelli, G. Iolascon, F. Gimigliano, M. Muratore, P. Camboa, O. Borgia, and et al. Incidence and costs of hip fractures compared to acute myocardial infarction in the Italian population: a 4-year survey Osteoporos. Int. 18 2007 211 219
11. L. Melton, E. Chrischilles, C. Cooper, A. Lane, and B. Riggs Perspective. How many women have osteoporosis? J. Bone Miner. Res. 7 1992 1005 1010
12. R. Burge, B. Dawson-Hughes, D. Solomon, J. Wong, A. King, and A. Tosteson Incidence and economic burden of osteoporosis related fractures in the United States, 2005-2025 J. Bone Miner. Res. 22 2007 465 475
13. V. Beral Million women study collaborators, breast cancer and hormone-replacement therapy in the million women study Lancet 362 2003 419 427
14. M.B. Zanchetta, M. Diehl, M. Buttazzoni, A. Galich, F. Silveira, C.E. Bogado, and et al. Assessment of bone microarchitecture in postmenopausal women on long term bisphosphonate therapy with atypical fractures of the femur J. Bone Miner. Res. 29 2013 999 1004
15. J. Pinkerton, and S. Thomas Use of SERMs for treatment in postmenopausal women J. Steroid Biochem. Mol. Biol. 142 2014 142 154
16. K. Cappuzzo, and J. Delafuente Teriparatide for severe osteoporosis Ann. Pharmacother. 38 2004 294 302
17. T. Ponnapakkam, R. Katikaneni, J. Sakon, R. Stratford, and R. Gensure Treating osteoporosis by targeting parathyroid hormone to bone Drug Discov. Today 19 2013 204 208
18. G.A. Rodan, and T.J. Martin Therapeutic approaches to bone diseases Science 289 2000 1508 1514
19. S.K. Chair, D. Burr, J. Cauley, D.W. Dempster, P.R. Ebeling, D. Felsenberg, and et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American society for bone and mineral research J. Bone Miner. Res. 22 2007 1479 1491
20. J.P. Bilezikian Combination anabolic and antiresorptive therapy for osteoporosis: opening the anabolic window Curr. Osteoporos. Rep. 6 2008 24 30
21. D.M. Black, S.L. Greenspan, K.E. Ensrud, L. Palermo, J.A. Mcgowan, T.F. Lang, and et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis N. Engl. J. Med. 349 2003 1207 1215
22. J.S. Finkelstein, A. Hayes, J.L. Hunzelman, J.J. Wyland, H. Lee, and A.R.M. Neer The effects of parathyroid hormone, alendronate, or both in men with osteoporosis N. Engl. J. Med. 349 2003 1216 1226
23. A.V. Uihlein, and B.Z. Leder Anabolic therapies for osteoporosis Endocrinol. Metab. Clin. N. Am. 41 2012 507 525
24. Y. Liu, J. Liu, and Y. Xia Chinese herbal medicines for treating osteoporosis Cochrane Database Syst. Rev. 2014 10.1002/14651858.CD005467.pub2
25. H. Xu, D. Lawson, A. Kras, and D. Ryan The use of preventive strategies for bone loss Am. J. Chin. Med. 2005 299 306
26. A. Maurice Drug combination strategies for osteoporosis Joint Bone Spine 73 2006 374 378
27. R. Marcus, and S. Majumdar The nature of osteoporosis R. Marcus, D. Feldman, J. Kelsey, Osteoporosis, Seconded 2001 Academic Press San Diego 3 17
28. R.T. Franceschi, C. Ge, G. Xiao, H. Roca, and D. Jiang Transcriptional regulation of osteoblasts Ann. N. Y. Acad. Sci. 1116 2007 196 207
29. I. Bremner, and J. Beattie Copper and zinc metabolism in health and disease: speciation and interactions Proc. Nutr. Soc. 54 1995 489 499
30. J.R. Farley, S.L. Hall, M.A. Tanner, and J.E. Wergedal Specific activity of skeletal alkaline phosphatase in human osteoblast-line cells regulated by phosphate, phosphate esters, and phosphate analogs and release of alkaline phosphatase activity inversely regulated by calcium J. Bone Miner. Res. 9 1994 497 508
31. M. Balcerzak, E. Hamade, L. Zhang, S. Pikula, G. Azzar, J. Radisson, and et al. The roles of annexins and alkaline phosphatase in mineralization process Acta Biochim. Pol. 50 2003 1019 1038
32. G.S. Stein, J.B. Lian, and T.A. Owen Relationship of cell growth to the regulation of tissue-specific gene expression during osteoblast differentiation FASEB J. 4 1990 3111 3123
33. C. Wennberg, L. Hessle, P. Lundberg, S. Mauro, S. Narisawa, U.H. Lerner, and et al. Functional characterization of osteoblasts and osteoclasts from alkaline phosphatase knockout mice J. Bone Miner. Res. 15 2000 1879 1888
34. J.A.R. Gordon, C.E. Tye, A.V. Sampaio, T.M. Underhill, G.K. Hunter, and H.A. Goldberg Bone sialoprotein expression enhances osteoblast differentiation and matrix mineralization in vitro Bone 41 2007 462 473
35. P. Ducy, C. Desbois, B. Boyce, G. Pinero, B. Story, C. Dunstan, and et al. Increased bone formation in osteocalcin-deficient mice Nature 382 1996 448 452
36. K. Merry, R. Dodds, A. Littlewood, and M. Gowen Expression of osteopontin mRNA by osteoclasts and osteoblasts in modelling adult human bone J. Cell Sci. 104 1993 1013 1020
37. S.R. Rittling, H.N. Matsumoto, M.D. Mckee, A. Nanci, X.R. An, K.E. Novick, and et al. Mice lacking osteopontin show normal development and bone structure but display altered osteoclast formation in vitro J. Bone Miner. Res. 13 1998 1101 1111
38. H. Yoshitake, S.R. Rittling, D.T. Denhardt, and M. Noda Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption Proc. Natl. Acad. Sci. U. S. A. 96 1999 8156 8160
39. M. Ishijima, K. Tsuji, S.R. Rittling, T. Yamashita, H. Kurosawa, D.T. Denhardt, and et al. Resistance to unloading-induced three-dimensional bone loss in osteopontin-deficient mice J. Bone Miner. Res. 17 2002 661 667
40. M. Mizuno, and Y. Kuboki Osteoblast-related gene expression of bone marrow cells during the osteoblastic differentiation induced by type I collagen J. Biochem. 129 2001 133 138
41. S. Mathews, R. Bhonde, P.K. Gupta, and S. Totey Extracellular matrix protein mediated regulation of the osteoblast differentiation of bone marrow derived human mesenchymal stem cells Differentiation 84 2012 185 192
42. E. Hinoi, S. Fujimori, L. Wang, H. Hojo, K. Uno, and Y. Yoneda Nrf2 negatively regulates osteoblast differentiation via interfering with Runx2-dependent transcriptional activation J. Biol. Chem. 281 2006 18015 18024
43. J. Pratap, M. Galindo, S.K. Zaid, D. Vradii, B.M. Bhat, J.A. Robinson, and et al. Cell growth regulatory role of Runx2 during proliferative expansion of preosteoblasts Cancer Res. 63 2003 5357 5362
44. V. Geoffroy, M. Kneissel, B. Fournier, A. Boyde, and P. Matthias High bone resorption in adult aging transgenic mice overexpressing cbfa1/runx2 in cells of the osteoblastic lineage Mol. Cell. Biol. 22 2002 6222 6233
45. R.T. Franceschi, G. Xiao, D. Jiang, R. Gopalakrishnan, S. Yang, and E. Reith Multiple signaling pathways converge on the Cbfa1/Runx2 transcription factor to regulate osteoblast differentiation Connect. Tissue Res. 44 2003 109 116
46. P. Ducy, R. Zhang, V. Geoffroy, A.L. Ridall, and G. Karsenty Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation Cell 89 1997 747 754
47. K. Nakashima, X. Zhou, G. Kunkel, Z. Zhang, J.M. Deng, R.R. Behringer, and et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation Cell 108 2002 17 29
48. M.F. Pittenger, A.M. Mackay, S.C. Beck, R.K. Jaiswal, R. Douglas, J.D. Mosca, and et al. Multilineage potential of adult human mesenchymal stem cells Science 284 1999 143 147
49. D. Prusty, B.H. Park, K.E. Davis, and S.R. Farmer Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma) and C/EBPalpha gene expression during the differentiation of 3T3-L1 preadipocytes J. Biol. Chem. 277 2002 46226 46232
50. L. Song, J. Zhao, X. Zhang, H. Li, and Y. Zhou Icariin induces osteoblast proliferation, differentiation and mineralization through estrogenre ceptor-mediated ERK and JNK signal activation Eur. J. Pharmacol. 714 2013 15 22
51. L. Li, Z. Zeng, and G. Cai Comparison of neoeriocitrin and naringin on proliferation and osteogenic differentiation in MC3T3-E1 Phytomedicine 18 2011 985 989
52. H.Y. Yoon, S.I. Yun, B.Y. Kim, Q. Jin, E.R. Woo, S.Y. Jeong, and et al. Poncirin promotes osteoblast differentiation but inhibits adipocyte differentiation in mesenchymal stem cells Eur. J. Pharmacol. 664 2011 54 59
53. S. Srivastava, R. Bankar, and P. Roy Assessment of the role of flavonoids for inducing osteoblast differentiation in isolated mouse bone marrow derived mesenchymal stem cells Phytomedicine 20 2013 683 690
54. M.A. Satué, M.D.M. Arriero, M. Monjo, and J.M. Ramis Quercitrin and taxifolin stimulate osteoblast differentiation in MC3T3-E1 cells and inhibit osteoclastogenesis in RAW 264.7 cells Biochem. Pharmacol. 86 2013 1476 1486
55. H. Sun, L. Li, A. Zhang, N. Zhang, H. Lv, W. Sun, and et al. Protective effects of sweroside on human MG-63 cells and rat osteoblasts Fitoterapia 84 2013 174 179
56. W.S. Simonet, D.L. Lacey, C.R. Dunstan, M. Kelley, M.S. Chang, R. Lüthy, and et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density Cell 89 1997 309 319
57. D.L. Lacey, E. Timms, H.L. Tan, M.J. Kelley, C.R. Dunstan, T. Burgess, and et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation Cell 93 1998 165 176
58. T. Ikeda, M. Utsuyama, and K. Hirokawa Expression profiles of receptor activator of nuclear factor κB ligand, receptor activator of nuclear factor κB, and osteoprotegerin messenger RNA in aged and ovariectomized rat bones J. Bone Miner. Res. 16 2001 1416 1425
59. K. S The OPG/RANKL/RANK system Endocrinology 142 2001 5050 5055
60. F. Li, Y. Yang, P. Zhu, W. Chen, D. Qi, X. Shi, and et al. Echinacoside promotes bone regeneration by increasing OPG/RANKL ratio in MC3T3-E1 cells Fitoterapia 83 2012 1443 1450
61. H. Xiao, Q. Gao, Y. Zhang, K.C. Wong, Y. Dai, X. Yao, and et al. Vanillic acid exerts oestrogen-like activities in osteoblast-like UMR 106 cells through MAP kinase (MEK/ERK)-mediated ER signaling pathway J. Steroid Biochem. Mol. Biol. 144 2014 382 391
62. M.B. Kim, Y. Song, and J.K. Hwang Kirenol stimulates osteoblast differentiation through activation of the BMP and Wnt/β-catenin signaling pathways in MC3T3-E1 cells Fitoterapia 98 2014 59 65
63. E.M. Choi Honokiol isolated from Magnolia officinalis stimulates osteoblast function and inhibits the release of bone-resorbing mediators Int. Immunopharmacol. 11 2011 1541 1545
64. Y.S. Lee, and E.M. Choi Apocynin stimulates osteoblast differentiation and inhibits bone-resorbing mediators in MC3T3-E1 cells Cell. Immunol. 270 2011 224 229
65. W. Tiyasatkulkovit, N. Charoenphandhu, K. Wongdee, J. Thongbunchoo, N. Krishnamra, and S. Malaivijitnondc Upregulation of osteoblastic differentiation marker mRNA expression in osteoblast-like UMR106 cells by puerarin and phytoestrogens from Pueraria mirifica Phytomedicine 19 2012 1147 1155
66. T.P. Hsieh, S.Y. Sheu, J.S. Sun, M.H. Chen, and M.H. Liu Icariin isolated from epimedium pubescens regulates osteoblasts anabolism through BMP-2, SMAD4, and Cbfa1 expression Phytomedicine 17 2010 414 423
67. H.H. Xiao, C.Y. Fung, S.K. Mok, K.C. Wong, M.X. Ho, X.L. Wang, and et al. Flavonoids from herba epimedii selectively activate estrogen receptor alpha (ERα) andstimulate ER-dependent osteoblastic functionsin UMR-106 cells J. Steroid Biochem. Mol. Biol. 143 2014 141 151
68. L. Chang, and M. Karin Mammalian MAP kinase signalling cascades Nature 410 2001 37 40
69. T. Akune, S. Ohba, S. Kamekura, M. Yamaguchi, U. Chung, N. Kubota, and et al. PPARγ insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors J. Clin. Investig. 113 2004 846 855
70. E. Hu, J. Kim, P. Sarraf, and B. Spiegelman Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma Science 274 1996 2100 2103
71. M. Aouadi, K. Laurent, M. Prot, Y.L.M. Brustel, B. Binétruy, and F. Bost Inhibition of p38 MAPK increases adipogenesis from embryonic to adult stages Diabetes 55 2006 281 289
72. M.B. Greenblatt, J.H. Shim, W. Zou, D. Sitara, M. Schweitzer, D. Hu, and et al. The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice J. Clin. Investig. 120 2010 2457 2473
73. C. Ge, G. Xiao, D. Jiang, and R.T. Franceschi Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development J. Cell Biol. 176 2007 709 718
74. X. Wang, C.H. Goh, and B. Li p38 Mitogen-activated protein kinase regulates osteoblast differentiation through osterix Endocrinology 148 2007 1629 1637
75. C.H. Lee, Y.L. Huang, J.F. Liao, and W.F. Chiou Ugonin K promotes osteoblastic differentiation and mineralization by activation of p38 MAPK- and ERK-mediated expression of Runx2 and osterix Eur. J. Pharmacol. 668 2011 383 389
76. M.J. Don, L.C. Lin, and W.F. Chiou Neobavaisoflavone stimulates osteogenesis via p38-mediated up-regulation of transcription factors and osteoid genes expression in MC3T3-E1 cells Phytomedicine 19 2012 551 561
77. D. Xu, L. Xu, C. Zhou, W.Y.W. Lee, T. Wu, L. Cui, and et al. Salvianolic acid B promotes osteogenesis of human mesenchymalstem cells through activating ERK signaling pathway Int. J. Biochem. Cell Biol. 51 2014 1 9
78. Y.S. Lee, and E.M. Choi Costunolide stimulates the function of osteoblastic MC3T3-E1 cells Int. Immunopharmacol. 11 2011 712 718
79. C.H. Tang, R.S. Yang, M.Y. Chien, C.C. Chen, and W.M. Fu Enhancement of bone morphogenetic protein-2 expression and bone formation by coumarin derivatives via p38 and ERK-dependent pathway in osteoblasts Eur. J. Pharmacol. 579 2008 40 49
80. J.H. Kwak, S.R. Lee, H.J. Park, H.E. Byun, E.H. Sohn, B.O. Kim, and et al. Kobophenol A enhances proliferation of human osteoblast-like cells with activation of the p38 pathway Int. Immunopharmacol. 17 2013 704 713
81. T. Sakou, T. Onishi, T. Yamamoto, T. Nagamine, T.K. Sampath, and P.T. Dijke Localization of Smads, the TGF-β family intracellular signaling components during endochondral ossification J. Bone Miner. Res. 14 1999 1145 1152
82. A. Nohe, E. Keating, P. Knaus, and N.O. Petersen Signal transduction of bone morphogenetic protein receptors Cell. Signal. 16 2004 291 299
83. U. Styrkarsdottir, J.B. Cazier, A. Kong, O. Rolfsson, H. Larsen, E. Bjarnadottir, and et al. Linkage of osteoporosis to chromosome 20p12 and association to BMP2 PLoS Biol. 1 2003 e69
84. M.H. Lee, Y.J. Kim, H.J. Kim, H.D. Park, A.R. Kang, H.M. Kyung, and et al. 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 2003 34387 34394
85. T.F. Day, X. Guo, L.G. Beal, and Y. Yang Wnt/β-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis Dev. Cell 8 2005 739 750
86. M. Shtutman, J. Zhurinsky, I. Simcha, C. Albanese, M. D'amico, R. Pestell, and et al. The cyclin D1 gene is a target of the β-catenin/LEF-1 pathway Proc. Natl. Acad. Sci. U. S. A. 96 1999 5522 5527
87. N. Ghosh-Choudhury, C.C. Mandal, and G.G. Choudhury Statin-induced Ras activation integrates the phosphatidylinositol 3-kinase signal to Akt and MAPK for bone morphogenetic protein-2 expression in osteoblast differentiation J. Biol. Chem. 282 2007 4983 4993
88. J.Q. Feng, L. Xing, J.H. Zhang, M. Zhao, D. Horn, J. Chan, and et al. NF-κB specifically activates BMP-2 gene expression in growth plate chondrocytes in vivo and in a chondrocyte cell line in vitro J. Biol. Chem. 278 2003 29130 29135
89. W. Liang, M. Lin, X. Li, C. Li, B. Gao, H. Gan, and et al. Icariin promotes bone formation via the BMP-2/Smad4 signal transduction pathway in the hFOB 1.19 human osteoblastic cell line Int. J. Mol. Med. 30 2012 889 895
90. J.B. Wu, Y.C. Fong, H.Y. Tsai, Y.F. Chen, M. Tsuzuki, and C.H. Tang Naringin-induced bone morphogenetic protein-2 expression via PI3K, Akt, c-Fos/c-Jun and AP-1 pathway in osteoblasts Eur. J. Pharmacol. 588 2008 333 341
91. D.Z. Tang, F. Yang, Z. Yang, J. Huang, Q. Shi, D. Chen, and et al. Psoralen stimulates osteoblast differentiation through activation of BMP signaling Biochem. Biophys. Res. Commun. 405 2011 256 261
92. D.Z. Tang, W. Hou, Q. Zhou, M. Zhang, J. Holz, T.J. Sheu, and et al. Osthole stimulates osteoblast differentiation and bone formation by activation of b-catenin-BMP signaling J. Bone Miner. Res. 25 2010 1234 1245
93. S.U. Lee, H.K. Shin, Y.K. Min, and S.H. Kim Emodin accelerates osteoblast differentiation through phosphatidylinositol 3-kinase activation and bone morphogenetic protein-2 gene expression Int. Immunopharmacol. 8 2008 741 747
94. J. Chen, N. Zhang, G. Mao, X. He, Y. Zhan, H. Deng, and et al. Salidroside stimulates osteoblast differentiation through BMP signaling pathway Food Chem. Toxicol. 62 2013 499 505
95. T. Kihara, S. Ichikawa, T. Yonezawa, J.-W. Lee, T. Akihisa, J.T. Woo, and et al. Acerogenin A, a natural compound isolated from Acer nikoense Maxim, stimulates osteoblast differentiation through bone morphogenetic protein action Biochem. Biophys. Res. Commun. 406 2011 211 217
96. K.D. Wright, V. Cavailles, S.A. Fuqua, V.C. Jordan, J.A. Katzenellenbogen, K.S. Korach, and et al. International union of pharmacology. LXIV. Estrogen receptors Pharmacol. Rev. 58 2006 773 781
97. R.T. Turner, B.L. Riggs, and T.C. Spelsberg Skeletal effects of estrogen Endocr. Rev. 15 1994 275 300
98. B.J. Cheskis, J.G. Greger, S. Nagpal, and L.P. Freedman Signaling by estrogens J. Cell. Physiol. 213 2007 610 617
99. M. Marino, M. Pellegrini, P.L. Rosa, and F. Acconcia Susceptibility of estrogen receptor rapid responses to xenoestrogens: physiological outcomes Steroids 77 2012 910 917
100. S. Kato, H. Endoh, Y. Masuhiro, T. Kitamoto, S. Uchiyama, H. Sasaki, and et al. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase Science 270 1995 1491 1494
101. C.J. Gruberemail, D.M. Gruber, I.M.L. Gruber, F. Wieser, and J.C. Huber Anatomy of the estrogen response element Trends Endocrinol. Metab. 15 2004 73 78
102. A. Migliaccio, G. Castoria, M. Domenico, A. Falco, A. Bilancio, and F. Auricchio Src is an initial target of sex steroid hormone action Ann. N. Y. Acad. Sci. 963 2002 185 190
103. A. Zallone Direct and indirect estrogen actions on osteoblasts and osteoclasts Ann. N. Y. Acad. Sci. 1068 2006 173 179
104. S. Kousteni, T. Bellido, L.I. Plotkin, C.A. O'brien, D.L. Bodenner, L. Han, and et al. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity Cell 104 2001 719 730
105. C.H. Lee, Y.L. Huang, J.F. Liao, and W.F. Chiou Ugonin K-stimulated osteogenesis involves estrogen receptor-dependent activation of non-classical Src signaling pathway and classical pathway Eur. J. Pharmacol. 676 2012 26 33
106. M.H. Liao, Y.T. Tai, Y.G. Cherng, S.H. Liu, Y.A. Chang, P.I. Lin, and et al. Genistein induces oestrogen receptor-α gene expression in osteoblasts through the activation of mitogen-activated protein kinases/NF-κB/activator protein-1 and promotes cell mineralisation Br. J. Nutr. 111 2014 55 63
107. Y. Wang, W.L. Wang, W.L. Xie, L.Z. Li, J. Sun, W.J. Sun, and et al. Puerarin stimulates proliferation and differentiation and protects against celldeath in human osteoblastic MG-63 cells via ER-dependent MEK/ERK and PI3K/Akt activation Phytomedicine 20 2013 787 796
108. Z. Dai, Y. Li, L.D. Quarles, T. Song, W. Pan, H. Zhou, and et al. Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation Phytomedicine 14 2007 806 814
109. S.C. Manolagas From oestrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis Endocr. Rev. 31 2010 266 300
110. O.F. Sendur, Y. Turan, E. Tastaban, and M. Serter Antioxidant status in patients with osteoporosis: a controlled study Joint Bone Spine 76 2009 514 518
111. X. Bai, D. Lu, A. Liu, Z. Zhang, X. Li, Z. Zou, and et al. Reactive oxygen species stimulates receptor activator of NF-kappaB ligand expression in osteoblast J. Biol. Chem. 280 2005 17497 17506
112. H. Ha, H.B. Kwak, S.W. Lee, H.M. Jin, H.M. Kim, H.H. Kim, and et al. Reactive oxygen species mediate RANK signaling in osteoclasts Exp. Cell Res. 301 2004 119 127
113. K.H. Baek, K.W. Oh, W.Y. Lee, S.S. Lee, M.K. Kim, H.S. Kwon, and et al. Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures Calcif. Tissue Int. 87 2010 226 235
114. J.K. Zhang, L. Yang, G.L. Meng, J. Fan, J.Z. Chen, Q.Z. He, and et al. Protective effect of tetrahydroxystilbene glucoside against hydrogen peroxide-induced dysfunction and oxidative stress in osteoblastic MC3T3-E1 cells Eur. J. Pharmacol. 689 2012 31 37
115. Q. Huang, J. Shi, B. Gao, H.Y. Zhang, J. Fan, X.J. Li, and et al. Gastrodin: an ancient Chinese herbal medicine as a source for anti-osteoporosis agents via reducing reactive oxygen species Bone 73 2015 132 144
116. K.S. Suh, E.M. Choi, Y.S. Lee, and Y.S. Kim Protective effect of albiflorin against oxidative-stress-mediated toxicity in osteoblast-like MC3T3-E1 cells Fitoterapia 89 2013 33 41
117. Q. Huang, B. Gao, Q. Jie, B.Y. Wei, J. Fan, H.Y. Zhang, and et al. Ginsenoside-Rb2 displays anti-osteoporosis effects through reducing oxidative damage and bone-resorbing cytokines during osteogenesis Bone 66 2014 306 314
118. Q. Huang, B. Gao, L. Wang, H.Y. Zhang, X.J. Li, J. Shi, and et al. Ophiopogonin D: a new herbal agent against osteoporosis Bone 74 2015 18 28
119. S.J. Wimalawansa Nitric oxide: novel therapy for osteoporosis Expert. Opin. Pharmacother. 9 2008 3025 3044
120. S. Gutiérrez, J.P. Petiti, L.D.V. Sosa, L. Fozzatti, A.L.D. Paul, A.M. Masini-Repiso, and et al. 17β-Oestradiol acts as a negative modulator of insulin-induced lactotroph cell proliferation through oestrogen receptor alpha, via nitric oxide/guanylyl cyclase/cGMP Cell Prolif. 43 2010 505 514
121. L.C. Cantley The phosphoinositide 3-kinase pathway Science 296 2002 1655 1657
122. S. Dimmeler, I. Fleming, B. Fisslthaler, C. Hermann, R. Busse, and A.M. Zeiher Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation Nature 399 1999 601 605
123. S. Rokutanda, T. Fujita, N. Kanatani, C.A. Yoshida, H. Komori, W. Liu, and et al. Akt regulates skeletal development through GSK3, mTOR, and FoxOs Dev. Biol. 328 2009 78 93
124. Y.K. Zhai, X.Y. Guo, B.F. Ge, P. Zhen, X.N. Ma, J. Zhou, and et al. Icariin stimulates the osteogenic differentiation of rat bone marrow stromal cells via activating the PI3K-AKT-eNOS-NO-cGMP-PKG Bone 66 2014 189 198
125. S.R. Lee, J.H. Kwak, D.S. Park, and S. Pyo Protective effect of kobophenol A on nitric oxide-induced cell apoptosis in human osteoblast-like MG-63 cells: involvement of JNK, NF-κB and AP-1 pathways Int. Immunopharmacol. 11 2011 1251 1259