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Cordycepin (3′-deoxyadenosine) Down-Regulates the Proinflammatory Cytokines in Inflammation-Induced Osteoporosis Model

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Abstract

The effect of cordycepin (3′-deoxyadenosine) on inflammation-induced osteoporosis (IMO) was studied in this paper. After the rats were treated orally with cordycepin (20 mg/kg), serum osteocalcin (OC), homocysteine (HCY), C-terminal cross-linked telopeptides of collagen type I (CTX), maleic dialdehyde (MDA), polymorphonuclear cells (PMN), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), they were examined by ELISA or immunohistochemistry. The specimens from the liver were also processed for light microscopic examination. The IMO rats showed a significant increase in plasma CTX, MDA, PMN, IL-1β, TNF-α, and nitrate levels as well as a significant decrease in plasma OC. These changes were attenuated by cordycepin (20 mg/kg) supplementation in the IMO rats. Examination of the liver specimens revealed mononuclear cell infiltration in the portal areas in the IMO rats which was not detected in the cordycepin (20 mg/kg) rats. These results suggest that cordycepin may act as an anti-inflammatory agent in magnesium silicate-induced inflammation in osteoporosis.

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References

  1. Yun, A.J., and P.Y. Lee. 2004. Maldaptation of the link between inflammation and bone turnover may be a key determinant of osteoporosis. Medical Hypotheses 63: 532–537.

    Article  PubMed  Google Scholar 

  2. Mitra, D., D.M. Elvins, D.J. Speden, and A.J. Collins. 2000. The prevalence of vertebral fractures in mild ankylosing spondylitis and their relationship to bone mineral density. Rheumatology (Oxford) 39(1): 85–89.

    Article  CAS  Google Scholar 

  3. Moschen, A.R., A. Kaser, B. Enrich, et al. 2005. The RANKL/OPG system is activated in inflammatory bowel diseases and relates to the state or bone loss. Gut 54: 479–487.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Saidenberg-Kermanach, N., M. Cohen-Solal, N. Bessis, M.C. De Vernejoul, and M.C. Boissier. 2004. Role for osteoprotegerin in rheumatoid inflammation. Joint Bone Spine 71: 9–13.

    Article  Google Scholar 

  5. Lorenzo, J. 2000. Interactions between immune and bone cells: new insights with many remaining questions. Journal of Clinical Investigation 106: 749–752.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Teitelbaum, S.L. 2000. Bone resorption by osteoclasts. Science 289: 1504–1508.

    Article  CAS  PubMed  Google Scholar 

  7. Kim, H., A.S. Naura, Y. Errami, J. Ju, and A.H. Boulares. 2011. Cordycepin blocks lung injury-associated inflammation and promotes BRCA1-deficient breast cancer cell killing by effectively inhibiting PARP. Molecular Medicine 17: 893–900.

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Kim, H.G., B. Shrestha, S.Y. Lim, D.H. Yoon, W.C. Chang, D.J. Shin, et al. 2006. Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NFkappaB through Akt and p38 inhibition in RAW 264.7 macrophage cells. European Journal of Pharmacology 545: 192–199.

    Article  CAS  PubMed  Google Scholar 

  9. Noh, E.M., J.S. Kim, H. Hur, B.H. Park, E.K. Song, M.K. Han, et al. 2009. Cordycepin inhibits IL-1beta-induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts. Rheumatology (Oxford) 48: 45–48.

    Article  CAS  Google Scholar 

  10. Ni, H., X.H. Zhou, H.H. Li, and W.F. Huang. 2009. Column chromatographic extraction and preparation of cordycepin from cordyceps militaris waster medium. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences 877: 2135–2141.

    Article  CAS  PubMed  Google Scholar 

  11. Minne, H.W., J. Pfeilschifter, S. Scharla, S. Mutschelknauss, A. Schwarz, B. Krempien, and R. Ziegler. 1984. Inflammation-mediated osteopenia in the rat: a new animal model for pathological loss of bone mass. Endocrinology 115: 50–54.

    Article  CAS  PubMed  Google Scholar 

  12. Grabowski, P.S., A.J. England, R. Dykhuizen, M. Copland, N. Benjamin, D.M. Reid, and S.H. Ralston. 1996. Elevated nitric oxide production in rheumatoid arthritis: detection using the fasting urinary nitrate:creatinine ratio. Arthritis and Rheumatism 39: 643–647.

    Article  CAS  PubMed  Google Scholar 

  13. Ohshima, H., I.M. Brouet, T. Bandaletova, H. Adachi, S. Oguchi, S. Iida, Y. Kurashima, Y. Morishita, T. Sugimura, and H. Esumi. 1992. Polyclonal antibody against an inducible form of nitric oxide synthase purified from the liver of rats treated with propionibacterium acnes and lipopolysaccharide. Biochemical and Biophysical Research Communications 187: 1291–1297.

    Article  CAS  PubMed  Google Scholar 

  14. Deodhar, A.A., and A.D. Woolf. 1996. Bone mass measurement and bone metabolism in rheumatoid arthritis: a review. British Journal of Rheumatology 35: 309–322.

    Article  CAS  PubMed  Google Scholar 

  15. Andreassen, H., J. Rungby, J.F. Dahlerup, and L. Mosekilde. 1997. Inflammatory bowel disease and osteoporosis. Scandinavian Journal of Gastroenterology 32: 1247–1255.

    Article  CAS  PubMed  Google Scholar 

  16. Minne, H.W., J. Pfeilschifter, S. Scharla, et al. 1984. Inflammation-mediated osteopenia in the rat: a new animal model for pathological loss of bone mass. Endocrinology 115: 50–54.

    Article  CAS  PubMed  Google Scholar 

  17. Minne, H.W., J. Pfeilschifter, S. Scharla, S. Mutschelknauss, A. Schwarz, B. Krempien, and R. Ziegler. 1984. Inflammation-mediated osteopenia in the rat: a new animal model for pathological loss of bone mass. Endocrinology 115: 50–54.

    Article  CAS  PubMed  Google Scholar 

  18. Pfeilschifter, J., C. Wuster, M. Vogel, B. Enderes, R. Ziegler, and H.W. Minne. 1987. Inflammation-mediated osteopenia (IMO) during acute inflammation in rats is due to a transient inhibition of bone formation. Calcified Tissue International 41: 321–325.

    Article  CAS  PubMed  Google Scholar 

  19. Polak-Jonkisz, D., and D. Zwolinska. 1998. Osteocalcin as a biochemical marker of bone turnover. Nephrology 4: 339–346.

    Article  CAS  Google Scholar 

  20. Koh, J.M., Y.S. Lee, Y.S. Kim, et al. 2006. Homocysteine enhances bone resorption by stimulation of osteoclast formation and activity through increased intracellular ROS generation. Journal of Bone and Mineral Research 21: 1003–1011.

    Article  CAS  PubMed  Google Scholar 

  21. Herrmann, M., N. Umanskaya, B. Wildemann, et al. 2008. Stimulation of osteoblast activity by homocysteine. Journal of Cellular and Molecular Medicine 12: 1205–1210.

    Article  CAS  PubMed  Google Scholar 

  22. Burgeson, R.E. 1988. New collagens, new concepts. Annual Review of Cell Biology 4: 552–577.

    Article  Google Scholar 

  23. Guerrero, R., M.A. Diaz Martin, E.M. Diaz Diego, et al. 1996. New biochemical markers of bone resorption derived from collagen breakdown in the study of postmenopausal osteoporosis. Osteoporosis International 6: 297–302.

    Article  CAS  PubMed  Google Scholar 

  24. Sánchez-Rodríguez, M.A., M. Ruiz-Ramos, E. Correa-Muñoz, and V.M. Mendoza-Núñez. 2007. Oxidative stress as a risk factor for osteoporosis in elderly Mexicans as characterized by antioxidant enzymes. BMC Musculoskeletal Disorders 8: 124.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Widomski, D., D.J. Fretland, A.F. Gasiecki, and P.W. Collins. 1997. The prostaglandin analogs, misoprostol and SC-46275, potently inhibit cytokine release from activated human monocytes. Immunopharmacology and Immunotoxicology 19: 165–174.

    Article  CAS  PubMed  Google Scholar 

  26. Zoppo, G.J., G.W. Schmid-Schonbein, E. Mori, B.R. Copeland, and C.M. Chang. 1991. Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. Stroke 22: 1276–1283.

    Article  PubMed  Google Scholar 

  27. Hartl, R., L. Schurer, G.W. Schmid-Schonbein, and G.J. Zoppo. 1996. Experimental antileukocyte interventions in cerebral ischemia. Journal of Cerebral Blood Flow and Metabolism 16: 1108–1119.

    Article  CAS  PubMed  Google Scholar 

  28. Pacifici, R. 1996. Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. Journal of Bone and Mineral Research 11: 1043–1051.

    Article  CAS  PubMed  Google Scholar 

  29. Poli, V., R. Balena, E. Fattori, A. Markatos, M. Yamamoto, H. Tanaka, et al. 1994. Interleukin-6 deficient mice are protected from bone loss caused by estrogen depletion. EMBO Journal 13: 1189–1196.

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Ralston, S.H., L.P. Ho, M.H. Helfrich, P.S. Grabowski, P.W. Johnston, and N. Benjamin. 1995. Nitric oxide: a cytokine-induced regulator of bone resorption. Journal of Bone and Mineral Research 10: 1040–1049.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

    Da-wei Zhang, Wei Qi, Wei Lei & Guang-yue Zhao

  2. The Surgery Department of 520th Hospital of PLA, Mianyang, 621000, People’s Republic of China

    Wei Qi

  3. Department of Orthopedic Surgery, The NO.113 Hospital of PLA, Ningbo, 315000, People’s Republic of China

    Zhen-lin Wang

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  1. Da-wei Zhang
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  2. Zhen-lin Wang
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  3. Wei Qi
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  4. Wei Lei
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  5. Guang-yue Zhao
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Correspondence to Wei Lei or Guang-yue Zhao.

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Wei Lei and Guang-yue Zhao contributed equally to this work as cocorresponding authors

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Zhang, Dw., Wang, Zl., Qi, W. et al. Cordycepin (3′-deoxyadenosine) Down-Regulates the Proinflammatory Cytokines in Inflammation-Induced Osteoporosis Model. Inflammation 37, 1044–1049 (2014). https://doi.org/10.1007/s10753-014-9827-z

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