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Effect of Long-Term Green Tea Polyphenol Supplementation on Bone Architecture, Turnover, and Mechanical Properties in Middle-Aged Ovariectomized Rats

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Abstract

We investigated the effects of 6-month green tea polyphenols (GTP) supplementation on bone architecture, turnover, and mechanical properties in middle-aged ovariectomized (OVX) rats. Female rats were sham-operated (n = 39, 13/group) or OVX (n = 143, 13/group). Sham-control and OVX-control rats (n = 39) receiving no GTP were assigned for sample collection at baseline, 3, or 6 months. The remaining OVX rats (n = 104) were randomized to 0.15%, 0.5%, 1%, and 1.5% (g/dL) GTP for 3 or 6 months. Blood and bone samples were collected. Relative to the OVX-control group, GTP (1% and 1.5%) lowered serum procollagen type 1 N-terminal propeptide at 3 and 6 months, C-terminal telopeptides of type I collagen at 3 months, and insulin-like growth factor-I at 6 months. GTP did not affect bone mineral content and density. At 6 months, no dose of GTP positively affected trabecular bone volume based on microCT, but a higher cortical thickness and improved biomechanical properties of the femur mid-diaphysis was observed in the 1.5% GTP-treated group. At 3 and 6 months, GTP (0.5%, 1%, and 1.5%) had lower rates of trabecular bone formation and resorption than the OVX-control group, but the inhibitory effects of GTP on periosteal and endocortical bone mineralization and formation at the tibial midshaft were only evident at 3 months. GTP at higher doses suppressed bone turnover in the trabecular and cortical bone of OVX rats and resulted in improved cortical bone structural and biomechanical properties, although it was not effective in preventing the ovariectomy-induced dramatic cancellous bone loss.

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References

  1. Shen CL, Yeh JK, Stoecker BJ, Chyu MC, Wang JS (2009) Green tea polyphenols mitigate deterioration of bone microarchitecture in middle-aged female rats. Bone 44(4):684–690

    Article  CAS  PubMed  Google Scholar 

  2. Shen CL, Wang P, Guerrieri J, Yeh JK, Wang JS (2008) Protective effect of green tea polyphenols on bone loss in middle-aged female rats. Osteoporos Int 19(7):979–990

    Article  CAS  PubMed  Google Scholar 

  3. Shen CL, Cao JJ, Dagda RY, Tenner TE Jr, Chyu MC, Yeh JK (2011) Supplementation with green tea polyphenols improves bone microstructure and quality in aged, orchidectomized rats. Calcif Tissue Int 88(6):455–463

    Article  CAS  PubMed  Google Scholar 

  4. Shen CL, Yeh JK, Cao JJ, Tatum OL, Dagda RY, Wang J-S (2010) Green tea polyphenols mitigate bone loss of female rats in a chronic inflammation-induced bone loss model. J Nutr Biochem 21:968–974

    Article  CAS  PubMed  Google Scholar 

  5. Shen CL, Yeh JK, Samathanam C, Cao JJ, Stoecker BJ, Dagda RY, Chyu MC, Dunn DM, Wang JS (2011) Green tea polyphenols attenuate deterioration of bone microarchitecture in female rats with systemic chronic inflammation. Osteoporos Int 22:327–337

    Article  CAS  PubMed  Google Scholar 

  6. Shen CL, Syapin PJ, Graef JL, Smith BJ, Brackee G, Fowler AK, Segura I, Bergeson SE (2014) Alcohol-induced bone loss and quality during adolescence is improved by green tea polyphenols. J Clin Toxicol 7:004; Special issue title: Drug * Alcohol Abuse

    Google Scholar 

  7. Shen CL, Cao JJ, Dagda RY, Chanjaplammootil S, Lu C, Chyu MC, Gao W, Wang JS, Yeh JK (2012) Green tea polyphenols benefits body composition and improves bone quality in long-term high-fat diet-induced obese rats. Nutr Res 32(6):448–457

    Article  CAS  PubMed  Google Scholar 

  8. Shen CL, Chyu MC, Cao JJ, Yeh JK (2013) Green tea polyphenols improve bone microarchitecture in high-fat-diet-induced obese female rats through suppressing bone formation and erosion. J Med Food 16(5):421–427

    Article  CAS  PubMed  Google Scholar 

  9. Shen CL, Han J, Wang S, Chung E, Chyu MC, Cao JJ (2015) Green tea supplementation benefits body composition and improves bone properties in obese female rats fed with high-fat diet and caloric restricted diet. Nutr Res 35(12):1095–1105

    Article  CAS  PubMed  Google Scholar 

  10. Shen CL, Chyu MC, Yeh JK, Zhang Y, Pence BC, Felton CK (2012) Effect of green tea and Tai Chi on bone health in postmenopausal osteopenic women: a 6-month randomized placebo-controlled trial. Osteoporos Int 23(5):1541–1552

    Article  CAS  PubMed  Google Scholar 

  11. Dostal AM, Arikawa A, Espejo L, Kurzer MS (2016) Long-term supplementation of green tea extract does not modify adiposity or bone mineral density in a randomized trial of overweight and obese postmenopausal women. J Nutr 146(2):256–264

    Article  CAS  PubMed  Google Scholar 

  12. Iwaniec UT, Turner RT, Koo SI, Kaur R, Ho E, Wong CP et al (2009) Consumption of green tea extract results in osteopenia in growing male mice. J Nutr 139(10):1914–1919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Smith BJ, Bu SY, Wang Y, Rendina E, Lim YF, Marlow D, Clarke SL, Cullen DM, Lucas EA (2014) A comparative study of the bone metabolic response to dried plum supplementation and PTH treatment in adult, osteopenic ovariectomized rat. Bone 58:151–159

    Article  CAS  PubMed  Google Scholar 

  14. Nielsen FH (2004) Dietary fat composition modifies the effect of boron on bone characteristics and plasma lipids in rats. BioFactors 20:161–171

    Article  CAS  PubMed  Google Scholar 

  15. Sun YX, Li L, Corry KA, Zhang P, Yang Y, Himes E, Mihuti CL, Nelson C, Dai G, Li J (2015) Deletion of Nrf2 reduces skeletal mechanical properties and decreases load-driven bone formation. Bone 74:1–9

    Article  CAS  PubMed  Google Scholar 

  16. Parfitt AM, Drezner MJ, Glorieux FH, Kanis JA, Malluche H, Meunier PJ (1987) Bone histomorphometry: Standardization of nomenclature, symbols and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2:595–610

    Article  CAS  PubMed  Google Scholar 

  17. Shen CL, Brackee G, Song X, Tomison MD, Finckbone VL, Mitchell KT, Tang L, Chyu MC, Dunn DM, Wang JS (2017) Safety evaluation of green tea polyphenols consumption in middle-aged ovariectomized rat model. J Food Sci 82(9):2192–2220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Takeda S, Smith SY, Tamura T, Saito H, Takahashi F, Samadfam R, Haile S, Doyle N, Endo K (2015) Long-term treatment with eldecalcitol (1α, 25-dihydroxy-2β- (3-hydroxypropyloxy) vitamin D3) suppresses bone turnover and leads to prevention of bone loss and bone fragility in ovariectomized rats. Calcif Tissue Int 96(1):45–55

    Article  CAS  PubMed  Google Scholar 

  19. Tantikanlayaporn D, Wichit P, Weerachayaphorn J, Chairoungdua A, Chuncharunee A, Suksamrarn A, Piyachaturawat P (2013) Bone sparing effect of a novel phytoestrogen diarylheptanoid from Curcuma comosa Roxb. in ovariectomized rats. PLoS ONE 8(11):e78739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ferreri SL, Talish R, Trandafir T, Qin YX (2011) Mitigation of bone loss with ultrasound induced dynamic mechanical signals in an OVX induced rat model of osteopenia. Bone 48(5):1095–1102

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hamdi Kara I, Aydin S, Gemalmaz A, Aktürk Z, Yaman H, Bozdemir N et al (2007) Habitual tea drinking and bone mineral density in postmenopausal Turkish women: investigation of prevalence of postmenopausal osteoporosis in Turkey (IPPOT Study). Int J Vitam Nutr Res 77(6):389–397

    Article  CAS  PubMed  Google Scholar 

  22. Muraki S, Yamamoto S, Ishibashi H, Oka H, Yoshimura N, Kawaguchi H et al (2007) Diet and lifestyle associated with increased bone mineral density: cross-sectional study of Japanese elderly women at an osteoporosis outpatient clinic. J Orthop Sci 12(4):317–320

    Article  PubMed  Google Scholar 

  23. Hegarty VM, May HM, Khaw KT (2000) Tea drinking and bone mineral density in older women. Am J Clin Nutr 71(4):1003–1007

    Article  CAS  PubMed  Google Scholar 

  24. Wu CH, Yang YC, Yao WJ, Lu FH, Wu JS, Chang CJ (2002) Epidemiological evidence of increased bone mineral density in habitual tea drinkers. Arch Intern Med 162:1001–1006

    Article  PubMed  Google Scholar 

  25. Hoover PA, Webber CE, Beaumont LF, Blake JM (1996) Postmenopausal bone mineral density: relationship to calcium intake, calcium absorption, residual estrogen, body composition, and physical activity. Can J Physiol Pharmacol 74(8):911–917

    Article  CAS  PubMed  Google Scholar 

  26. Devine A, Hodgson JM, Dick IM, Prince RL (2007) Tea drinking is associated with benefits on bone density in older women. Am J Clin Nutr 86(4):1243–1247

    Article  CAS  PubMed  Google Scholar 

  27. Johnell O, Gullberg B, Kanis JA, Allander E, Elffors L, Dequeker J et al (1995) Risk factors for hip fracture in European women: the MEDOS Study. J Bone Miner Res 10:1802–1815

    Article  CAS  PubMed  Google Scholar 

  28. Kanis J, Johnell O, Gullberg B, Allander E, Elffors L, Ranstam J et al (1999) Risk factors for hip fracture in men from southern Europe: the MEDOS Study. Osteoporos Int 9:45–54

    Article  CAS  PubMed  Google Scholar 

  29. Chen X, Pettinger MB, Ritenbaugh C, LaCroix AZ, Robbins J, Caan BJ et al (2003) Habitual tea consumption and risk of osteoporosis: a prospective study in the women’s health initiative observational cohort. Am J Epidemiol 158:772–781

    Article  CAS  PubMed  Google Scholar 

  30. Shen CL, Yeh JK, Cao JJ, Wang JS (2009) Green tea and bone metabolism. Nutr Res 29(7):437–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Shen CL, Yeh JK, Cao JJ, Chyu MC, Wang JS (2011) Green tea and bone health: evidence from laboratory studies. Pharmacol Res 64(2):155–161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jin P, Li M, Xu G, Zhang K, Zheng LI, Zhao J (2015) Role of (−)-epigallocatechin-3-gallate in the osteogenic differentiation of human bone marrow mesenchymal stem cells: An enhancer or an inducer? Exp Ther Med 10(2):828–834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kaida K, Honda Y, Hashimoto Y, Tanaka M, Baba S (2015) Application of green tea catechin for inducing the osteogenic differentiation of human dedifferentiated fat cells in vitro. Int J Mol Sci 16(12):27988–28000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Nash LA, Ward WE (2016) Comparison of black, green and rooibos tea on osteoblast activity. Food Funct 7(2):1166–1175

    Article  CAS  PubMed  Google Scholar 

  35. Kamon M, Zhao R, Sakamoto K (2009) Green tea polyphenol (−)-epigallocatechin gallate suppressed the differentiation of murine osteoblastic MC3T3-E1 cells. Cell Biol Int 34:109–116

    PubMed  Google Scholar 

  36. Lee JH, Jin H, Shim HE, Kim HN, Ha H, Lee ZH (2010) Epigallocatechin-3-gallate inhibits osteoclastogenesis by down-regulating c-Fos expression and suppressing the nuclear factor-kappaB signal. Mol Pharmacol 77:17–25

    Article  CAS  PubMed  Google Scholar 

  37. Lin RW, Chen CH, Wang YH, Ho ML, Hung SH, Chen IS, Wang GJ (2009) (-)-Epigallocatechin gallate inhibition of osteoclastic differentiation via NF-kappaB. Biochem Biophys Res Commun 379:1033–1037

    Article  CAS  PubMed  Google Scholar 

  38. Wang Y, Bikle DD, Chang W (2013) Autocrine and paracrine actions of IGF-I signaling in skeletal development. Bone Res 1(3):249–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Crane JL, Cao X (2014) Function of matrix IGF-1 in coupling bone resorption and formation. J Mol Med (Berl) 92(2):107–115

    Article  CAS  Google Scholar 

  40. Turner RT, Hannon KS, Greene VS, Bell NH (1995) Prednisone inhibits formation of cortical bone in sham-operated and ovariectomized female rats. Calcif Tissue Int 56(4):311–315

    Article  CAS  PubMed  Google Scholar 

  41. Banfi G, Iorio EL, Corsi MM (2008) Oxidative stress, free radicals and bone remodeling. Clin Chem Lab Med 46(11):1550–1555

    Article  CAS  PubMed  Google Scholar 

  42. Pisoschi AM, Pop A (2015) The role of antioxidants in the chemistry of oxidative stress: a review. Eur J Med Chem 97:55–74

    Article  CAS  PubMed  Google Scholar 

  43. Lin RW, Chen CH, Wang YH, Ho ML, Hung SH, Chen IS, Wang GJ (2009) (–)-Epigallocatechin gallate inhibition of osteoclastic differentiation via NF-κB. Biochem Biophys Res Comm 379(4):1033–1037

    Article  CAS  PubMed  Google Scholar 

  44. Hider RC, Liu ZD, Khodr HH (2001) Metal chelation of polyphenols. Meth Enzymol 335:190–203

    Article  CAS  PubMed  Google Scholar 

  45. Kumamoto M, Sonda T, Nagayama K, Tabata M (2001) Effects of pH and metal ions on antioxidative activities of catechins. Biosci Biotechnol Biochem 65(1):126–132

    Article  CAS  PubMed  Google Scholar 

  46. Wasserman WW, Fahl WE (1997) Functional antioxidant responsive elements. Proc Natl Acad Sci USA 94(10):5361–5366

    Article  CAS  PubMed  Google Scholar 

  47. Choi EM, Hwang JK (2003) Effects of (+)-catechin on the function of osteoblastic cells. Biol Pharm Bull 26(4):523–526

    Article  CAS  PubMed  Google Scholar 

  48. Chen CH, Ho ML, Chang JK, Hung SH, Wang GJ (2005) Green tea catechin enhances osteogenesis in a bone marrow mesenchymal stem cell line. Osteoporos Int 16(12):2039–2045

    Article  CAS  PubMed  Google Scholar 

  49. Vali B, Rao LG, El-Sohemy A (2007) Epigallocatechin-3-gallate increases the formation of mineralized bone nodules by human osteoblast-like cells. J Nutr Biochem 18(5):341–347

    Article  CAS  PubMed  Google Scholar 

  50. Mount JG, Muzylak M, Allen S, Althnaian T, McGonnell I, Price J (2006) Evidence that the canonical Wnt signalling pathway regulates deer antler regeneration. Dev Dyn 235(5):1390–1399

    Article  CAS  PubMed  Google Scholar 

  51. Yamaguchi M, Jie Z. Effect of polyphenols on calcium content and alkaline phosphatase activity in rat femoral tissues in vitro. Biol Pharm Bull 2001;(12):1437–1439

  52. Hafeez BB, Ahmed S, Wang N, Gupta S, Zhang A, Haqqi TM (2006) Green tea polyphenols-induced apoptosis in human osteosarcoma SAOS-2 cells involves a caspase-dependent mechanism with downregulation of nuclear factor-κB. Toxicol Appl Pharmcol 216(1):11–19

    Article  CAS  Google Scholar 

  53. Tokuda H, Takai S, Hanai Y, Matsushima-Nishiwaki R, Hosoi T, Harada A, Ohta T, Kozawa O (2007) (–)-Epigallocatechin gallate suppresses endothelin-1-induced interleukin-6 synthesis in osteoblasts: Inhibition of p44/p42 MAP kinase activation. FEBS letters 581(7):1311–1316

    Article  CAS  PubMed  Google Scholar 

  54. Tokuda H, Takai S, Hanai Y, Matsushima-Nishiwaki R, Yamauchi J, Harada A, Hosoi T, Ohta T, Kozawa O (2008) (-)-Epigallocatechin gallate inhibits basic fibroblast growth factor-stimulated interleukin-6 synthesis in osteoblasts. Horm Metab Res 40(10):674–678

    Article  CAS  PubMed  Google Scholar 

  55. Hayashi K, Takai S, Matsushima-Nishiwaki R, Hanai Y, Kato K, Tokuda H, Kozawa O (2008) (−)-Epigallocatechin gallate reduces transforming growth factor β-stimulated HSP27 induction through the suppression of stress-activated protein kinase/c-Jun N-terminal kinase in osteoblasts. Life Sci 82(19):1012–1017

    Article  CAS  PubMed  Google Scholar 

  56. Nakagawa H, Hasumi K, Takami M, Aida-Hyugaji S, Woo J-T, Nagai K, Ishikawa T, Wachi M (2007) Identification of two biologically crucial hydroxyl groups of (−)-epigallocatechin gallate in osteoclast culture. Biochem Pharmacol 73(1):34–43

    Article  CAS  PubMed  Google Scholar 

  57. Nakagawa H, Wachi M, Woo J-T, Kato M, Kasai S, Takahashi F, Lee I-S, Nagai K (2002) Fenton reaction is primarily involved in a mechanism of (−)-epigallocatechin-3-gallate to induce osteoclastic cell death. Bioch Biophys Res Comm 292(1):94–101

    Article  CAS  Google Scholar 

  58. Yun JH, Pang EK, Kim CS, Yoo YJ, Cho KS, Chai JK, Kim CK, Choi SH (2004) Inhibitory effects of green tea polyphenol (−)-epigallocatechin gallate on the expression of matrix metalloproteinase-9 and on the formation of osteoclasts. J Periodontal Res 39(5):300–307

    Article  CAS  PubMed  Google Scholar 

  59. Delaissé J-M, Eeckhout Y, Vaes G (1986) Inhibition of bone resorption in culture by (+)-catechin. Biochem Pharmocol 35(18):3091–3094

    Article  Google Scholar 

  60. Nash LA, Ward WE (2015) Tea and bone health: findings from human studies, potential mechanisms, and identification of knowledge gaps. Crit Rev Food Sci Nutr 57(8):1603–1617

    Article  Google Scholar 

  61. Myers G, Prince RL, Kerr DA, Devine A, Woodman RJ, Lewis JR, Hodgson JM (2015) Tea and flavonoid intake predict osteoporotic fracture risk in elderly Australian women: a prospective study. Am J Clin Nutr 102(4):958–965

    Article  CAS  PubMed  Google Scholar 

  62. Chow HH, Cai Y, Hakim IA, Crowell JA, Shahi F, Brooks CA, Dorr RT, Hara Y, Alberts DS (2003) Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clin Cancer Res 9(9):3312–3319

    CAS  PubMed  Google Scholar 

  63. Shen CL, Brackee G, Song X, Tomison MD, Finckbone V, Mitchell KT, Tang L, Chyu MC, Dunn DM, Wang JS (2017) Safety evaluation of green tea polyphenols consumption in middle-aged ovariectomized rat model. J Food Sci 82(9):2192–2205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Rizzoli R, Reginster JY (2011) Adverse drug reactions to osteoporosis treatments. Expert Rev Clin Pharmacol 4(5):593–604

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by the National Center for Complementary and Integrative Health (NCCIH) of the National Institutes of Health under Grant U01AT006691 to Chwan-Li Shen. Jay Cao was supported by the Agricultural Research Service of the United States Department of Agriculture, #3062-51000-053-00D. We are grateful for the assistance of Dr. Gordon Brackee, Velvet Lee Finckbone, and Anna Rodriquez for sample collection. We thank Dr. Dale Dunn for his technical advising and support concerning histomorphometric analysis. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the NCCIH or the National Institutes of Health.

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Authors and Affiliations

  1. Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA

    Chwan-Li Shen, Michael D. Tomison & Ming-Chien Chyu

  2. Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA

    Brenda J. Smith & Maria F. Newhardt

  3. Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA

    Jiliang Li & Kylie A. Corry

  4. USDA ARS Grand Forks Human Nutrition Research Center, Grand Forks, ND, USA

    Jay J. Cao

  5. Department of Epidemiology and Biostatistics, University of Georgia, Athens, GA, USA

    Xiao Song

  6. Department of Environmental Health Science, University of Georgia, Athens, GA, USA

    Lili Tang & Jia-Sheng Wang

  7. Graduate Healthcare Engineering Option, Texas Tech University, Lubbock, TX, 79409, USA

    Ming-Chien Chyu

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  1. Chwan-Li Shen
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Chwan-Li Shen, Brenda J. Smith, Jay J. Cao, Jiliang Li, Xiao Song, Maria F. Newhardt, Kylie A. Corry, Michael D. Tomison, Lili Tang, Jia-Sheng Wang, and Ming-Chien Chyu declare that they have no conflict of interest.

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Shen, CL., Smith, B.J., Li, J. et al. Effect of Long-Term Green Tea Polyphenol Supplementation on Bone Architecture, Turnover, and Mechanical Properties in Middle-Aged Ovariectomized Rats. Calcif Tissue Int 104, 285–300 (2019). https://doi.org/10.1007/s00223-018-0489-y

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