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Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats

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Abstract

Summary

Treatment with molecular hydrogen alleviates microgravity-induced bone loss through abating oxidative stress, restoring osteoblastic differentiation, and suppressing osteoclast differentiation and osteoclastogenesis.

Introduction

Recently, it has been suggested that hydrogen gas exerts a therapeutic antioxidant activity by selectively reducing cytotoxic reactive oxygen species (ROS). The aim of the present study was to elucidate whether treatment with molecular hydrogen alleviated bone loss induced by modeled microgravity in rats.

Methods

Hindlimb suspension (HLS) and rotary wall vessel bioreactor were used to model microgravity in vivo and in vitro, respectively. Sprague–Dawley rats were exposed to HLS for 6 weeks to induced bone loss and simultaneously administrated with hydrogen water (HW). Then, we investigated the effects of incubation with hydrogen-rich medium (HRM) on MC3T3-E1 and RAW264.7 cells exposed to modeled microgravity.

Results

Treatment with HW alleviated HLS-induced reduction of bone mineral density, ultimate load, stiffness, and energy in femur and lumbar vertebra. Treatment with HW alleviated HLS-induced augmentation of malondialdehyde content and peroxynitrite content and reduction of total sulfhydryl content in femur and lumbar vertebra. In cultured MC3T3-E1 cells, incubation with HRM inhibited modeled microgravity-induced ROS formation, reduction of osteoblastic differentiation, increase of ratio of receptor activator of nuclear factor kappa B ligand to osteoprotegerin, inducible nitric oxide synthetase upregulation, and Erk1/2 phosphorylation. In cultured RAW264.7, incubation with HRM aggravated modeled microgravity-induced ROS formation, osteoclastic differentiation, and osteoclastogenesis.

Conclusion

Treatment with molecular hydrogen alleviates microgravity-induced bone loss in rats. Molecular hydrogen could thus be envisaged as a nutritional countermeasure for spaceflight but remains to be tested in humans.

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References

  1. 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 83:4289–4297

    Article  PubMed  CAS  Google Scholar 

  2. Fowler JF Jr (1991) Physiological changes during spaceflight. Cutis 48:291–295

    PubMed  Google Scholar 

  3. Vernikos J (1996) Human physiology in space. BioEssays 18:1029–1037

    Article  PubMed  CAS  Google Scholar 

  4. Riggs BL, Khosla S, Melton LJ 3rd (1998) A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res 13:763–773

    Article  PubMed  CAS  Google Scholar 

  5. Vico L, Lafage-Proust MH, Alexandre C (1998) Effects of gravitational changes on the bone system in vitro and in vivo. Bone 22:95S–100S

    Article  PubMed  CAS  Google Scholar 

  6. 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 21:311–315

    Article  PubMed  CAS  Google Scholar 

  7. 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 82:1478–1482

    Article  PubMed  CAS  Google Scholar 

  8. Chen HL, Qu LN, Li QD, Bi L, Huang ZM, Li YH (2009) Simulated microgravity-induced oxidative stress in different areas of rat brain. Sheng Li Xue Bao 61:108–114

    PubMed  CAS  Google Scholar 

  9. Momken I, Stevens L, Bergouignan A, Desplanches D, Rudwill F, Chery I, Zahariev A, Zahn S, Stein TP, Sebedio JL, Pujos-Guillot E, Falempin M, Simon C, Coxam V, Andrianjafiniony T, Gauquelin-Koch G, Picquet F, Blanc S (2011) Resveratrol prevents the wasting disorders of mechanical unloading by acting as a physical exercise mimetic in the rat. FASEB J 25:3646–3660

    Article  PubMed  CAS  Google Scholar 

  10. Shagimardanova EI, Gusev OA, Sychev VN, Levinskikh MA, Sharipova MR, Il'inskaia ON, Bingham G, Sugimoto M (2010) Stress response genes expression analysis of barley Hordeum vulgare under space flight environment. Mol Biol (Mosk) 44:831–838

    Article  CAS  Google Scholar 

  11. Bradamante S, Villa A, Versari S, Barenghi L, Orlandi I, Vai M (2010) Oxidative stress and alterations in actin cytoskeleton trigger glutathione efflux in Saccharomyces cerevisiae. Biochim Biophys Acta 1803:1376–1385

    Article  PubMed  CAS  Google Scholar 

  12. Wang J, Zhang J, Bai S, Wang G, Mu L, Sun B, Wang D, Kong Q, Liu Y, Yao X, Xu Y, Li H (2009) Simulated microgravity promotes cellular senescence via oxidant stress in rat PC12 cells. Neurochem Int 55:710–716

    Article  PubMed  CAS  Google Scholar 

  13. 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 1067:47

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  15. Kondo H, Yumoto K, Alwood JS, Mojarrab R, Wang A, Almeida EA, Searby ND, Limoli CL, Globus RK (2010) Oxidative stress and gamma radiation-induced cancellous bone loss with musculoskeletal disuse. J Appl Physiol 108:152–161

    Article  PubMed  Google Scholar 

  16. Wolf RL, Cauley JA, Pettinger M, Jackson R, Lacroix A, Leboff MS, Lewis CE, Nevitt MC, Simon JA, Stone KL, Wactawski-Wende J (2005) Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women’s Health Initiative. Am J Clin Nutr 82:581–588

    PubMed  CAS  Google Scholar 

  17. Talaulikar VS, Chambers T, Manyonda I (2012) Exploiting the antioxidant potential of a common vitamin: could vitamin C prevent postmenopausal osteoporosis? J Obstet Gynaecol Res 38:253–257

    Article  PubMed  CAS  Google Scholar 

  18. Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S (2007) Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 13:688–694

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  20. Mosekilde L, Danielsen CC, Knudsen UB (1993) The effects of aging and ovariectomy on the vertebral bone mass and biomechanical properties of mature rats. Bone 14:1–6

    Article  PubMed  CAS  Google Scholar 

  21. Katsumata T, Nakamura T, Ohnishi H, Sakurawa T (1995) Intermittent cyclical etidronate treatment maintains the mass, structure and the mechanical property of bone in ovariectomized rats. J Bone Miner Res 10:921–931

    Article  PubMed  CAS  Google Scholar 

  22. Elks CM, Mariappan N, Haque M, Guggilam A, Majid DS, Francis J (2009) Chronic NF-kB blockade reduces cytosolic and mitochondrial oxidative stress and attenuates renal injury and hypertension in SHR. Am J Physiol Renal Physiol 296:F298–305

    Article  PubMed  CAS  Google Scholar 

  23. 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 29:111–122

    Article  PubMed  CAS  Google Scholar 

  24. Hollander J, Gore M, Fiebig R, Mazzeo R, Ohishi S, Ohno H, Ji LL (1998) Spaceflight downregulates antioxidant defense systems in rat liver. Free Radic Biol Med 24:385–390

    Article  PubMed  CAS  Google Scholar 

  25. Reich KA, Chen YW, Thompson PD, Hoffman EP, Clarkson PM (2012) Forty-eight hours of unloading and 24 h of reloading lead to changes in global gene expression patterns related to ubiquitination and oxidative stress in humans. J Appl Physiol 109:1404–1415

    Article  Google Scholar 

  26. Al-Ajmi N, Braidman IP, Moore D (1996) Effect of clinostat rotation on differentiation of embryonic bone in vitro. Adv Space Res 17:189–192

    Article  PubMed  CAS  Google Scholar 

  27. Nakamura H, Kumei Y, Morita S, Shimokawa H, Ohya K, Shinomiya K (2003) Suppression of osteoblastic phenotypes and modulation of pro- and anti-apoptotic features in normal human osteoblastic cells under a vector-averaged gravity condition. J Med Dent Sci 50:167–176

    PubMed  Google Scholar 

  28. Sarkar D, Nagaya T, Koga K, Nomura Y, Gruener R, Seo H (2000) Culture in vector-averaged gravity under clinostat rotation results in apoptosis of osteoblastic ROS 17/2.8 cells. J Bone Miner Res 15:489–498

    Article  PubMed  CAS  Google Scholar 

  29. Qian A, Di S, Gao X, Zhang W, Tian Z, Li J, Hu L, Yang P, Yin D, Shang P (2009) cDNA microarray reveals the alterations of cytoskeleton-related genes in osteoblast under high magneto-gravitational environment. Acta Biochim Biophys Sin 41:561–577

    Article  PubMed  CAS  Google Scholar 

  30. Rucci N, Rufo A, Alamanou M, Teti A (2007) Modeled microgravity stimulates osteoclastogenesis and bone resorption by increasing osteoblast RANKL/OPG ratio. J Cell Biochem 100:464–473

    Article  PubMed  CAS  Google Scholar 

  31. Boehrs J, Zaharias RS, Laffoon J, Ko YJ, Schneider GB (2008) Three-dimensional culture environments enhance osteoblast differentiation. J Prosthodont 17:517–521

    Article  PubMed  Google Scholar 

  32. Makihira S, Kawahara Y, Yuge L, Mine Y, Nikawa H (2008) Impact of the microgravity environment in a 3-dimensional clinostat on osteoblast- and osteoclast-like cells. Cell Biol Int 32:1176–1181

    Article  PubMed  CAS  Google Scholar 

  33. Ontiveros C, McCabe LR (2003) Simulated microgravity suppresses osteoblast phenotype, Runx2 levels and AP-1 transactivation. J Cell Biochem 88:427–437

    Article  PubMed  CAS  Google Scholar 

  34. Pardo SJ, Patel MJ, Sykes MC, Platt MO, Boyd NL, Sorescu GP, Xu M, van Loon JJ, Wang MD, Jo H (2005) Simulated microgravity using the Random Positioning Machine inhibits differentiation and alters gene expression profiles of 2T3 preosteoblasts. Am J Physiol Cell Physiol 288:C1211–1121

    Article  PubMed  CAS  Google Scholar 

  35. 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 397:315–323

    Article  PubMed  CAS  Google Scholar 

  36. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319

    Article  PubMed  CAS  Google Scholar 

  37. 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 20:345–357

    Article  PubMed  CAS  Google Scholar 

  38. Zhang R, Ran HH, Ma J, Bai YG, Lin LJ (2012) NAD(P)H oxidase inhibiting with apocynin improved vascular reactivity in tail-suspended hindlimb unweighting rat. J Physiol Biochem 68:99–105

    Article  PubMed  CAS  Google Scholar 

  39. Wang MT, Huang Z, Yang R, Su J, Mai YX, Zhou HC, Deng WM (2010) Disruption of the microfilament cytoskeleton induced by simulated microgravity affects NO/NOS system of osteoblasts. Nan Fang Yi Ke Da Xue Xue Bao 30:1658–1662

    PubMed  Google Scholar 

  40. Yan L, Yinghui T, Bo Y, Gang Z, Xian X, Lu Z (2011) Effect of calcitonin gene-related peptide on nitric oxide production in osteoblasts: an experimental study. Cell Biol Int 35:757–765

    Article  PubMed  CAS  Google Scholar 

  41. Chen RM, Chen TL, Chiu WT, Chang CC (2005) Molecular mechanism of nitric oxide-induced osteoblast apoptosis. J Orthop Res 23:462–468

    Article  PubMed  CAS  Google Scholar 

  42. Park BG, Yoo CI, Kim HT, Kwon CH, Kim YK (2005) Role of mitogen-activated protein kinases in hydrogen peroxide-induced cell death in osteoblastic cells. Toxicol 215:115–125

    Article  CAS  Google Scholar 

  43. Lee NK, Choi YG, Baik JY, Han SY, Jeong DW, Bae YS, Kim N, Lee SY (2005) A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood 106:852–859

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Emergency, The Military General Hospital of Beijing PLA, Beijing, 100700, China

    Y. Sun, D. M. Chen & R. B. Zhou

  2. Department of Orthopaedics, 94 Hospital of PLA, Nanchang, 330002, China

    F. Shuang

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Correspondence to R. B. Zhou.

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Sun, Y., Shuang, F., Chen, D.M. et al. Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats. Osteoporos Int 24, 969–978 (2013). https://doi.org/10.1007/s00198-012-2028-4

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  • DOI: https://doi.org/10.1007/s00198-012-2028-4

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