Top

Osteoporosis International

Published in:

01-11-2015 | Original Article

Attenuation of hind-limb suspension-induced bone loss by curcumin is associated with reduced oxidative stress and increased vitamin D receptor expression

Authors: M. Xin, Y. Yang, D. Zhang, J. Wang, S. Chen, D. Zhou

Published in: Osteoporosis International | Issue 11/2015

Abstract

Summary

Treatment with curcumin attenuated modeled microgravity-induced bone loss, possibly through abating oxidative stress and activating vitamin D receptor. Curcumin might be an effective countermeasure for microgravity-induced bone loss but remains to be tested in humans.

Introduction

Bone loss is one of the most important complications for human crewmembers who are exposed to long-term microgravity in space and also for bedridden people. The aim of the current study was to elucidate whether treatment with curcumin attenuated bone loss induced by microgravity.

Methods

We used hind-limb suspension (HLS) and rotary wall vessel bioreactor (RWVB) to model microgravity in vivo and in vitro, respectively. We investigated the effects of curcumin consumption (40 mg kg⁻¹ body weight day⁻¹, via daily oral gavages) on Sprague–Dawley (SD) rats exposed to HLS for 6 weeks. Then, we investigated the effects of incubation with curcumin (4 μM) on MC3T3-E1 and RAW264.7 cells cultured in RWVB.

Results

Curcumin alleviated HLS-induced reduction of bone mineral density in tibiae and preserved bone structure in tibiae and mechanical strength in femurs. Curcumin alleviated HLS-induced oxidative stress marked by reduced malondialdehyde content and increased total sulfhydryl content in femurs. In cultured MC3T3-E1 cells, curcumin inhibited modeled microgravity-induced reactive oxygen species (ROS) formation and enhanced osteoblastic differentiation. In cultured RAW264.7 cells, curcumin reduced modeled microgravity-induced ROS formation and attenuated osteoclastogenesis. In addition, curcumin upregulated vitamin D receptor (VDR) expression in femurs of rats exposed to HLS and MC3T3-E1 cells exposed to modeled microgravity.

Conclusion

Curcumin alleviated HLS-induced bone loss in rats, possibly via suppressing oxidative stress and upregulating VDR expression.

Available only for authorised users

Blanc S, Normand S, Ritz P, Pachiaudi C, Vico L, Gharib C, Gauquelin-Koch G (1998) Energy and water metabolism, body composition, and hormonal changes induced by 42 days of enforced inactivity and simulated weightlessness. J Clin Endocrinol Metab 83:4289–4297PubMed

Kim H, Iwasaki K, Miyake T, Shiozawa T, Nozaki S, Yajima K (2003) Changes in bone turnover markers during 14-day 6 degrees head-down bed rest. J Bone Miner Metab 21:311–315CrossRefPubMed

Zhang DW, Fu M, Gao SH, Liu JL (2013) Curcumin and diabetes: a systematic review. Evid Based Complement Alternat Med 2013:636053PubMedCentralPubMed

Zhou H, Beevers CS, Huang S (2011) The targets of curcumin. Curr Drug Targets 12:332–347PubMedCentralCrossRefPubMed

French DL, Muir JM, Webber CE (2008) The ovariectomized, mature rat model of postmenopausal osteoporosis: an assessment of the bone sparing effects of curcumin. Phytomedicine 15:1069–1078CrossRefPubMed

Hussan F, Ibraheem NG, Kamarudin TA, Shuid AN, Soelaiman IN, Othman F (2012) Curcumin protects against ovariectomy-induced bone changes in rat model. Evid Based Complement Alternat Med 2012:174916PubMedCentralPubMed

Zhou T, Chen D, Li Q, Sun X, Song Y, Wang C (2013) Curcumin inhibits inflammatory response and bone loss during experimental periodontitis in rats. Acta Odontol Scand 71:349–356CrossRefPubMed

Yang MW, Wang TH, Yan PP, Chu LW, Yu J, Gao ZD, Li YZ, Guo BL (2011) Curcumin improves bone microarchitecture and enhances mineral density in APP/PS1 transgenic mice. Phytomedicine 18:205–213CrossRefPubMed

Dinkova-Kostova AT, Talalay P (2008) Direct and indirect antioxidant properties of inducers of cytoprotective proteins. Mol Nutr Food Res 52:S128–S138PubMed

10.

Bartik L, Whitfield GK, Kaczmarska M, Lowmiller CL, Moffet EW, Furmick JK, Hernandez Z, Haussler CA, Haussler MR, Jurutka PW (2010) Curcumin: a novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention. J Nutr Biochem 21:1153–1161PubMedCentralCrossRefPubMed

11.

Zayzafoon M, Gathings WE, Mcdonald JM (2004) Modeled microgravity inhibits osteogenic differentiation of human mesenchymal stem cells and increases adipogenesis. Endocrinology 145:2421–2432CrossRefPubMed

12.

Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R (2010) Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res 25:1468–1486CrossRefPubMed

13.

Saxena R, Pan G, Dohm ED, McDonald JM (2011) Modeled microgravity and hindlimb unloading sensitize osteoclast precursors to RANKL mediated osteoclastogenesis. J Bone Miner Metab 29:111–122PubMedCentralCrossRefPubMed

14.

Rai B, Kaur J, Catalina M, Anand SC, Jacobs R, Teughels W (2011) Effect of simulated microgravity on salivary and serum oxidants, antioxidants, and periodontal status. J Periodontol 82:1478–1482CrossRefPubMed

15.

Sun Y, Shuang F, Chen DM, Zhou RB (2013) Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats. Osteoporos Int 24:969–978CrossRefPubMed

16.

Linnane AW, Eastwood H (2006) Cellular redox regulation and prooxidant signaling systems, a new perspective on the free radical theory of aging. Ann N Y Acad Sci 1067:47CrossRefPubMed

17.

Sendur OF, Turan Y, Tastaban E, Serter M (2009) Antioxidant status in patients with osteoporosis, a controlled study. Joint Bone Spine 76:514CrossRefPubMed

18.

Hemeida RA, Mohafez OM (2008) Curcumin attenuates methotraxate-induced hepatic oxidative damage in rats. J Egypt Natl Cancer Inst 20:141–148

19.

Fleenor BS, Sindler AL, Marvi NK, Howell KL, Zigler ML, Yoshizawa M, Seals DR (2013) Curcumin ameliorates arterial dysfunction and oxidative stress with aging. Exp Gerontol 48:269–276PubMedCentralCrossRefPubMed

20.

Moran JM, Roncero-Martin R, Rodriguez-Velasco FJ, Calderon-Garcia JF, Rey-Sanchez P, Vera V, Canal-Macias ML, Pedrera-Zamorano JD (2012) Effects of curcumin on the proliferation and mineralization of human osteoblast-like cells: implications of nitric oxide. Int J Mol Sci 13:16104–16118PubMedCentralCrossRefPubMed

21.

Notoya M, Nishimura H, Woo JT, Nagai K, Ishihara Y, Hagiwara H (2006) Curcumin inhibits the proliferation and mineralization of cultured osteoblasts. Eur J Pharmacol 534:55–62CrossRefPubMed

22.

Chan WH, Wu HY, Chang WH (2006) Dosage effects of curcumin on cell death types in a human osteoblast cell line. Food Chem Toxicol 44:1362–1371CrossRefPubMed

23.

Gu Q, Cai Y, Huang C, Shi Q, Yang H (2012) Curcumin increases rat mesenchymal stem cell osteoblast differentiation but inhibits adipocyte differentiation. Pharmacogn Mag 8:202–208PubMedCentralCrossRefPubMed

24.

Moon HJ, Ko WK, Han SW, Kim DS, Hwang YS, Park HK, Kwon IK (2012) Antioxidants, like coenzyme Q10, selenite, and curcumin, inhibited osteoclast differentiation by suppressing reactive oxygen species generation. Biochem Biophys Res Commun 418:247–253CrossRefPubMed

25.

Kim JH, Gupta SC, Park B, Yadav VR, Aggarwal BB (2012) Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis. Mol Nutr Food Res 56:454–465PubMedCentralCrossRefPubMed

26.

Park SK, Oh S, Shin HK, Kim SH, Ham J, Song JS, Lee S (2011) Synthesis of substituted triazolyl curcumin mimics that inhibit RANKL-induced osteoclastogenesis. Bioorg Med Chem Lett 21:3573–3577CrossRefPubMed

27.

Oh S, Kyung TW, Choi HS (2008) Curcumin inhibits osteoclastogenesis by decreasing receptor activator of nuclear factor-kappaB ligand (RANKL) in bone marrow stromal cells. Mol Cells 26:486–489PubMed

28.

Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G, Itie A, Khoo W, Wakeham A, Dunstan CR, Lacey DL, Mak TW, Boyle WJ, Penninger JM (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397:315–323CrossRefPubMed

29.

Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20:345–357CrossRefPubMed

30.

Zerwekh JE, Odvina CV, Wuermser L-A, Pak CYC (2007) Reduction of renal stone risk by potassiummagnesium citrate during 5 weeks of bed rest. J Urol 177:2179–2184CrossRefPubMed

31.

Zerwekh JE, Ruml LA, Gottschalk F, Pak CYC (1998) The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects. J Bone Miner Res 13:1594–1601CrossRefPubMed

32.

Smith SM, Wastney ME, Morukov BV, Larina IM, Nyquist LE, Abrams SA, Taran EN, Shih CY, Nillen JL, Davis-Street JE, Rice BL, Lane HW (1999) Calcium metabolism before, during, and after a 3-mo spaceflight: kinetic and biochemical changes. Am J Physiol 277:R1–R10CrossRefPubMed

33.

Zittermann A, Heer M, Caillot-Augusso P, Rettberg P, Scheld K, Drummer C, Alexandre C, Horneck G, Vorobiev D, Stehle P (2000) Microgravity inhibits intestinal calcium absorption as shown by a stable strontium test. Eur J Clin Investig 30:1036–1043CrossRef

34.

Yoshida T, Stern PH (2012) How vitamin D works on bone. Endocrinol Metab Clin N Am 41:557–569CrossRef

35.

Pike JW, Yamamoto H, Shevde NK (2002) Vitamin D receptormediated gene regulation mechanisms and current concepts of vitamin D analog selectivity. Adv Ren Replace Ther 9:168–174CrossRefPubMed

36.

Narayanan R, Smith CL, Weigel NL (2002) Vector-averaged gravity-induced changes in cell signaling and vitamin D receptor activity in MG-63 cells are reversed by a 1,25-(OH)2D3 analog, EB1089. Bone 31:381–388CrossRefPubMed

37.

Chandran B, Goel A (2012) A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother Res 26:1719–1725CrossRefPubMed

38.

Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21:2895–2900PubMed

39.

Bielak-Zmijewska A, Koronkiewicz M, Skierski J, Piwocka K, Radziszewska E, Sikora E (2000) Effect of curcumin on the apoptosis of rodent and human nonproliferating and proliferating lymphoid cells. Nutr Cancer 38:131–138CrossRefPubMed

40.

Mosieniak G, Adamowicz M, Alster O, Jaskowiak H, Szczepankiewicz AA, Wilczynski GM, Ciechomska IA, Sikora E (2012) Curcumin induces permanent growth arrest of human colon cancer cells: link between senescence and autophagy. Mech Ageing Dev 133:444–455CrossRefPubMed

41.

Hendrayani SF, Al-Khalaf HH, Aboussekhra A (2013) Curcumin triggers p16-dependent senescence in active breast cancer-associated fibroblasts and suppresses their paracrine procarcinogenic effects. Neoplasia 15:631–640PubMedCentralCrossRefPubMed

42.

Grabowska W, Kucharewicz K, Wnuk M, Lewinska A, Suszek M, Przybylska D, Mosieniak G, Sikora E, Bielak-Zmijewska A (2015) Curcumin induces senescence of primary human cells building the vasculature in a DNA damage and ATM-independent manner. Age (Dordr) 37:9744CrossRef

Title: Attenuation of hind-limb suspension-induced bone loss by curcumin is associated with reduced oxidative stress and increased vitamin D receptor expression
Authors: M. Xin
Y. Yang
D. Zhang
J. Wang
S. Chen
D. Zhou
Publication date: 01-11-2015
Publisher: Springer London
Published in: Osteoporosis International / Issue 11/2015
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-015-3153-7

At a glance: The STEP trials

Springer Medicine

Attenuation of hind-limb suspension-induced bone loss by curcumin is associated with reduced oxidative stress and increased vitamin D receptor expression

Abstract

Summary

Introduction

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 11/2015

The burden of osteoporotic hip fractures in Portugal: costs, health related quality of life and mortality

Erratum to: Taxonomy of rare genetic metabolic bone disorders

Reply to “Thoracolumbar fascia injury associated with residual back pain after percutaneous vertebroplasty: a compelling study”

Bone histomorphometry in diabetes mellitus

Diagnosis of vertebral fractures using a low-dose biplanar imaging system

FRAX and the effect of teriparatide on vertebral and non-vertebral fracture