Skip to main content

Advertisement

Log in

Resveratrol prevents ovariectomy-induced bone quality deterioration by improving the microarchitectural and biophysicochemical properties of bone

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

Osteoporosis is a major health problem that is very common worldwide and is characterized by both low bone density and deterioration in bone quality. New treatment options without side effects have become an active area of research in recent years. This study was designed to investigate the preventive effects of resveratrol on bone quality deterioration caused by ovariectomy.

Materials and Methods

Sixty rats were randomly divided into five groups (12 animals per group): Control, Sham-operated (SHAM), ovariectomized (OVX), OVX + Resveratrol-40 mg/kg/day (OVX + Res40), OVX + Resveratrol-80 mg/kg/day (OVX + Res80). Resveratrol was administered by oral gavage (40 and 80 mg/kg/day) for ten weeks. Micro-CT measurements, biomechanical testing, Raman spectroscopy analysis, and RT-PCR analysis were performed. ALP, OCN, TAS, and TOS levels were also measured from blood serum.

Results

Bone strength, bone volume/total volume, trabecular volume, and trabecular thickness were higher in the OVX + RES-80 group than in the OVX group. Resveratrol increased osteogenic differentiation, as the expression of osteogenic markers ALP, Col1A1, Runx2, OPG, OCN increased in both OVX + RES-80 and OVX + RES-40 groups compared to the OVX group. 80 mg/kg/day resveratrol administration decreased the levels of ALP, OCN and TOS in ovariectomized rats. Raman spectroscopy findings showed a preventive effect of resveratrol administration against ovariectomy-induced deterioration in biophysiochemical properties of bone tissue.

Conclusion

This study revealed that administration of different doses of 80 mg/kg/day and 40 mg/kg/day of resveratrol had protective effects on bone quality deterioration caused by ovariectomy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Tou JC (2015) Resveratrol supplementation affects bone acquisition and osteoporosis: Pre-clinical evidence toward translational diet therapy. Biochim Biophys Acta 1852:1186–1194. https://doi.org/10.1016/j.bbadis.2014.10.003

    Article  CAS  PubMed  Google Scholar 

  2. Gullberg B, Johnell O, Kanis JA (1997) World-wide projections for hip fracture. Osteoporos Int 7:407–413. https://doi.org/10.1007/pl00004148

    Article  CAS  PubMed  Google Scholar 

  3. Zeng Q, Li N, Wang Q, Feng J, Sun D, Zhang Q, Huang J, Wen Q, Hu R, Wang L, Ma Y, Fu X, Dong S, Cheng X (2019) The prevalence of osteoporosis in china, a nationwide, multicenter DXA Survey. J Bone Miner Res 34:1789–1797. https://doi.org/10.1002/jbmr.3757

    Article  PubMed  Google Scholar 

  4. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A (2007) Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res 22:465–475. https://doi.org/10.1359/jbmr.061113

    Article  PubMed  Google Scholar 

  5. Holroyd C, Cooper C, Dennison E (2008) Epidemiology of osteoporosis. Best Pract Res Clin Endocrinol Metab 22:671–685. https://doi.org/10.1016/j.beem.2008.06.001

    Article  PubMed  Google Scholar 

  6. Beral V, Reeves G, Bull D, Green J (2011) Breast cancer risk in relation to the interval between menopause and starting hormone therapy. J Natl Cancer Inst 103:296–305. https://doi.org/10.1093/jnci/djq527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chlebowski RT, Anderson G, Manson JE, Pettinger M, Yasmeen S, Lane D, Langer RD, Hubbell FA, McTiernan A, Hendrix S, Schenken R, Stefanick ML (2010) Estrogen alone in postmenopausal women and breast cancer detection by means of mammography and breast biopsy. J Clin Oncol 28:2690–2697. https://doi.org/10.1200/JCO.2009.24.8799

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zhao M, Liu J, Zhang X, Peng L, Li C, Peng S (2009) 3D QSAR of novel estrogen-RGD peptide conjugates: getting insight into structural dependence of anti-osteoporosis activity and side effect of estrogen in ERT. Bioorg Med Chem 17:3680–3689. https://doi.org/10.1016/j.bmc.2009.03.057

    Article  CAS  PubMed  Google Scholar 

  9. Smoliga JM, Baur JA, Hausenblas HA (2011) Resveratrol and health–a comprehensive review of human clinical trials. Mol Nutr Food Res 55:1129–1141. https://doi.org/10.1002/mnfr.201100143

    Article  CAS  PubMed  Google Scholar 

  10. Novelle MG, Wahl D, Dieguez C, Bernier M, de Cabo R (2015) Resveratrol supplementation: Where are we now and where should we go? Ageing Res Rev 21:1–15. https://doi.org/10.1016/j.arr.2015.01.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Feng J, Liu S, Ma S, Zhao J, Zhang W, Qi W, Cao P, Wang Z, Lei W (2014) Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-kappaB signaling pathway. Acta Biochim Biophys Sin (Shanghai) 46:1024–1033. https://doi.org/10.1093/abbs/gmu103

    Article  CAS  PubMed  Google Scholar 

  12. Zhao M, Ko SY, Garrett IR, Mundy GR, Gutierrez GE, Edwards JR (2018) The polyphenol resveratrol promotes skeletal growth in mice through a sirtuin 1-bone morphogenic protein 2 longevity axis. Br J Pharmacol 175:4183–4192. https://doi.org/10.1111/bph.14477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yu T, Wang Z, You X, Zhou H, He W, Li B, Xia J, Zhu H, Zhao Y, Yu G, Xiong Y, Yang Y (2020) Resveratrol promotes osteogenesis and alleviates osteoporosis by inhibiting p53. Aging (Albany NY) 12:10359–10369. https://doi.org/10.18632/aging.103262

    Article  CAS  PubMed  Google Scholar 

  14. Shakibaei M, Buhrmann C, Mobasheri A (2011) Resveratrol-mediated SIRT-1 interactions with p300 modulate receptor activator of NF-kappaB ligand (RANKL) activation of NF-kappaB signaling and inhibit osteoclastogenesis in bone-derived cells. J Biol Chem 286:11492–11505. https://doi.org/10.1074/jbc.M110.198713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Feng YL, Jiang XT, Ma FF, Han J, Tang XL (2018) Resveratrol prevents osteoporosis by upregulating FoxO1 transcriptional activity. Int J Mol Med 41:202–212. https://doi.org/10.3892/ijmm.2017.3208

    Article  CAS  PubMed  Google Scholar 

  16. Bhattarai G, Poudel SB, Kook SH, Lee JC (2016) Resveratrol prevents alveolar bone loss in an experimental rat model of periodontitis. Acta Biomater 29:398–408. https://doi.org/10.1016/j.actbio.2015.10.031

    Article  CAS  PubMed  Google Scholar 

  17. Omnia Ameen RIYaYMN (2020) Activation of FoxO1/SIRT1/RANKL/OPG pathway may underlie the therapeutic effects of resveratrol on aging-dependent male osteoporosis. BMC musculoskel disord. 21:389

    Google Scholar 

  18. Lin Q, Huang YM, Xiao BX, Ren GF (2005) Effects of resveratrol on bone mineral density in ovarectomized rats. Int J Biomed Sci 1:76–81

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang X, Chen L, Peng W (2017) Protective effects of resveratrol on osteoporosis via activation of the SIRT1-NF-kappaB signaling pathway in rats. Exp Ther Med 14:5032–5038. https://doi.org/10.3892/etm.2017.5147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang W, Zhang LM, Guo C, Han JF (2020) Resveratrol promotes osteoblastic differentiation in a rat model of postmenopausal osteoporosis by regulating autophagy. Nutr Metab (Lond) 17:29. https://doi.org/10.1186/s12986-020-00449-9

    Article  CAS  PubMed  Google Scholar 

  21. Zhao H, Li X, Li N, Liu T, Liu J, Li Z, Xiao H, Li J (2014) Long-term resveratrol treatment prevents ovariectomy-induced osteopenia in rats without hyperplastic effects on the uterus. Br J Nutr 111:836–846. https://doi.org/10.1017/S0007114513003115

    Article  CAS  PubMed  Google Scholar 

  22. Jiang Y, Luo W, Wang B, Wang X, Gong P, Xiong Y (2020) Resveratrol promotes osteogenesis via activating SIRT1/FoxO1 pathway in osteoporosis mice. Life Sci 246:117422. https://doi.org/10.1016/j.lfs.2020.117422

    Article  CAS  PubMed  Google Scholar 

  23. Khera A, Kanta P, Kalra J, Dumir D (2019) Resveratrol restores the level of key inflammatory cytokines and RANKL/OPG ratio in the femur of rat osteoporosis model. J Women Aging 31:540–552. https://doi.org/10.1080/08952841.2018.1522126

    Article  PubMed  Google Scholar 

  24. Zhao L, Wang Y, Wang Z, Xu Z, Zhang Q, Yin M (2015) Effects of dietary resveratrol on excess-iron-induced bone loss via antioxidative character. J Nutr Biochem 26:1174–1182. https://doi.org/10.1016/j.jnutbio.2015.05.009

    Article  CAS  PubMed  Google Scholar 

  25. Durbin SM, Jackson JR, Ryan MJ, Gigliotti JC, Alway SE, Tou JC (2014) Resveratrol supplementation preserves long bone mass, microstructure, and strength in hindlimb-suspended old male rats. J Bone Miner Metab 32:38–47. https://doi.org/10.1007/s00774-013-0469-2

    Article  CAS  PubMed  Google Scholar 

  26. Karimian E, Tamm C, Chagin AS, Samuelsson K, Kjartansdottir KR, Ohlsson C, Savendahl L (2013) Resveratrol treatment delays growth plate fusion and improves bone growth in female rabbits. PLoS ONE 8:e67859. https://doi.org/10.1371/journal.pone.0067859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Nair AB, Jacob S (2016) A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 7:27–31. https://doi.org/10.4103/0976-0105.177703

    Article  PubMed  PubMed Central  Google Scholar 

  28. Erel O (2005) A new automated colorimetric method for measuring total oxidant status. Clin Biochem 38:1103–1111. https://doi.org/10.1016/j.clinbiochem.2005.08.008

    Article  CAS  PubMed  Google Scholar 

  29. Unal M, Ahmed R, Mahadevan-Jansen A, Nyman JS (2021) Compositional assessment of bone by Raman spectroscopy. Analyst 146:7464–7490. https://doi.org/10.1039/d1an01560e

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Unal M, Uppuganti S, Timur S, Mahadevan-Jansen A, Akkus O, Nyman JS (2019) Assessing matrix quality by Raman spectroscopy helps predict fracture toughness of human cortical bone. Sci Rep 9:7195. https://doi.org/10.1038/s41598-019-43542-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Donmez BO, Ozdemir S, Sarikanat M, Yaras N, Koc P, Demir N, Karayalcin B, Oguz N (2012) Effect of angiotensin II type 1 receptor blocker on osteoporotic rat femurs. Pharmacol Rep 64:878–888. https://doi.org/10.1016/s1734-1140(12)70882-4

    Article  CAS  PubMed  Google Scholar 

  32. Turner CH (2002) Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteoporos Int 13:97–104. https://doi.org/10.1007/s001980200000

    Article  CAS  PubMed  Google Scholar 

  33. Donmez BO, Ozturk N, Sarikanat M, Oguz N, Sari R, Ozdemir S (2014) Sodium tungstate alleviates biomechanical properties of diabetic rat femur via modulation of oxidative stress. Gen Physiol Biophys 33:443–452. https://doi.org/10.4149/gpb_2014020

    Article  CAS  PubMed  Google Scholar 

  34. Lee AM, Shandala T, Nguyen L, Muhlhausler BS, Chen KM, Howe PR, Xian CJ (2014) Effects of resveratrol supplementation on bone growth in young rats and microarchitecture and remodeling in ageing rats. Nutrients 6:5871–5887. https://doi.org/10.3390/nu6125871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Li Y, Tseng WJ, de Bakker CMJ, Zhao H, Chung R, Liu XS (2021) Peak trabecular bone microstructure predicts rate of estrogen-deficiency-induced bone loss in rats. Bone 145:115862. https://doi.org/10.1016/j.bone.2021.115862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mandair GS, Morris MD (2015) Contributions of Raman spectroscopy to the understanding of bone strength. Bonekey Rep 4:620. https://doi.org/10.1038/bonekey.2014.115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Paschalis EP, Gamsjaeger S, Klaushofer K (2017) Vibrational spectroscopic techniques to assess bone quality. Osteoporos Int 28:2275–2291. https://doi.org/10.1007/s00198-017-4019-y

    Article  CAS  PubMed  Google Scholar 

  38. Unal M (2020) Letter to the Editor. Connect Tissue Res 61:420–422. https://doi.org/10.1080/03008207.2019.1666113

    Article  PubMed  Google Scholar 

  39. Unal M, Uppuganti S, Leverant CJ, Creecy A, Granke M, Voziyan P, Nyman JS (2018) Assessing glycation-mediated changes in human cortical bone with Raman spectroscopy. J Biophotonics. 11:201700352. https://doi.org/10.1002/jbio.201700352

    Article  CAS  Google Scholar 

  40. Unal M, Jung H, Akkus O (2016) Novel Raman Spectroscopic Biomarkers Indicate That Postyield Damage Denatures Bone’s Collagen. J Bone Miner Res 31:1015–1025. https://doi.org/10.1002/jbmr.2768

    Article  CAS  PubMed  Google Scholar 

  41. Paschalis EP, Shane E, Lyritis G, Skarantavos G, Mendelsohn R, Boskey AL (2004) Bone fragility and collagen cross-links. J Bone Miner Res 19:2000–2004. https://doi.org/10.1359/JBMR.040820

    Article  PubMed  Google Scholar 

  42. Wang X, Xu H, Huang Y, Gu S, Jiang JX (2016) Coupling Effect of Water and Proteoglycans on the In Situ Toughness of Bone. J Bone Miner Res 31:1026–1029. https://doi.org/10.1002/jbmr.2774

    Article  CAS  PubMed  Google Scholar 

  43. Unal M, Akkus O (2015) Raman spectral classification of mineral- and collagen-bound water’s associations to elastic and post-yield mechanical properties of cortical bone. Bone 81:315–326. https://doi.org/10.1016/j.bone.2015.07.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kawane T, Komori H, Liu W, Moriishi T, Miyazaki T, Mori M, Matsuo Y, Takada Y, Izumi S, Jiang Q, Nishimura R, Kawai Y, Komori T (2014) Dlx5 and mef2 regulate a novel runx2 enhancer for osteoblast-specific expression. J Bone Miner Res 29:1960–1969. https://doi.org/10.1002/jbmr.2240

    Article  CAS  PubMed  Google Scholar 

  45. Lin GL, Hankenson KD (2011) Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation. J Cell Biochem 112:3491–3501. https://doi.org/10.1002/jcb.23287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Liu Q, Zhang X, Jiao Y, Liu X, Wang Y, Li SL, Zhang W, Chen FM, Ding Y, Jiang C, Jin Z (2018) In vitro cell behaviors of bone mesenchymal stem cells derived from normal and postmenopausal osteoporotic rats. Int J Mol Med 41:669–678. https://doi.org/10.3892/ijmm.2017.3280

    Article  CAS  PubMed  Google Scholar 

  47. Gao Y, Patil S, Jia J (2021) The development of molecular biology of osteoporosis. Int J Mol Sci. https://doi.org/10.3390/ijms22158182

    Article  PubMed  PubMed Central  Google Scholar 

  48. Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342. https://doi.org/10.1038/nature01658

    Article  CAS  PubMed  Google Scholar 

  49. Walsh MC, Choi Y (2014) Biology of the RANKL-RANK-OPG System in Immunity, Bone, and Beyond. Front Immunol 5:511. https://doi.org/10.3389/fimmu.2014.00511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Minamizaki T, Sakurai K, Hayashi I, Toshishige M, Yoshioka H, Kozai K, Yoshiko Y (2020) Active sites of human MEPE-ASARM regulating bone matrix mineralization. Mol Cell Endocrinol. 517:110931. https://doi.org/10.1016/j.mce.2020.110931

    Article  CAS  PubMed  Google Scholar 

  51. Minamizaki T, Yoshiko Y (2015) The bioactive acidic serine- and aspartate-rich motif peptide. Curr Protein Pept Sci 16:196–202. https://doi.org/10.2174/1389203716666150206122839

    Article  CAS  PubMed  Google Scholar 

  52. Gowen LC, Petersen DN, Mansolf AL, Qi H, Stock JL, Tkalcevic GT, Simmons HA, Crawford DT, Chidsey-Frink KL, Ke HZ, McNeish JD, Brown TA (2003) Targeted disruption of the osteoblast/osteocyte factor 45 gene (OF45) results in increased bone formation and bone mass. J Biol Chem 278:1998–2007. https://doi.org/10.1074/jbc.M203250200

    Article  CAS  PubMed  Google Scholar 

  53. David V, Martin A, Hedge AM, Rowe PS (2009) Matrix extracellular phosphoglycoprotein (MEPE) is a new bone renal hormone and vascularization modulator. Endocrinology 150:4012–4023. https://doi.org/10.1210/en.2009-0216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Guo D, Keightley A, Guthrie J, Veno PA, Harris SE, Bonewald LF (2010) Identification of osteocyte-selective proteins. Proteomics 10:3688–3698. https://doi.org/10.1002/pmic.201000306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The study was part of Sevval Ozturk's master's thesis.

Funding

This study was supported by the Research Fund of Pamukkale University under project number: 2021SABE007.

Author information

Authors and Affiliations

Authors

Contributions

SO (Conceptualization, Methodology, Investigation, Visualization, Formal Analysis), IC (Investigation), FA (Investigation), ERK (Investigation, Writing-Review and Editing, Visualization), ACD (Writing-Review and Editing, Investigation), MO (Formal analysis, Investigation, Visualization), MU (Writing-Review and Editing, Investigation, Visualization), MS (Investigation), BOD (Writing-Review and Editing, Resources, Formal Analysis, Conceptualization, Project administration).

Corresponding author

Correspondence to Baris Ozgur Donmez.

Ethics declarations

Conflict of interest

None.

Ethical approval

The study was approved by the Animal Experimentation Ethical Committee of Pamukkale University (protocol number: 60758568–020/48556).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ozturk, S., Cuneyit, I., Altuntas, F. et al. Resveratrol prevents ovariectomy-induced bone quality deterioration by improving the microarchitectural and biophysicochemical properties of bone. J Bone Miner Metab 41, 443–456 (2023). https://doi.org/10.1007/s00774-023-01416-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-023-01416-z

Keywords

Navigation