The Effects of Simultaneous Administration of Granulocyte Colony-Stimulating Factor and Interferon-alpha on Osteoporosis

Document Type : Original Article (s)

Authors

1 Assistant Professor, Department of Biology, School of Science, Ferdowsi University of Mashhad, Mashhad, Iran

2 MSc Student, Department of Biology, School of Science, Ferdowsi University of Mashhad, Mashhad, Iran

3 Assistant Professor, Department of Clinical Sciences, School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran

4 Professor, Department of Biology, School of Science, Ferdowsi University of Mashhad, Mashhad, Iran

Abstract

Background: Bone loss is one of the major pathological symptoms of rheumatoid arthritis (RA) and some types of cancers. Granulocyte colony-stimulating factor (G-CSF) and interferon-alpha (IFN-α) are widely used in patients with cancer as a drug and o have been known to play a key role in rheumatoid arthritis. This study aimed to investigate the effects of these factors on osteoporosis.Methods: 28 mouse (Mus musculus, male, and eight weeks of age) were divided into 4 groups of 7. They were injected subcutaneously with distilled water as control, 10 mg/kg IFN-α and 200 mg/kg G-CSF with or without 10 mg/kg IFN-α per day, for 28 days. After killing mice, standardized radiographs were taken from femur bones and the Image J program was used for measurement of the femoral bone density. The total femoral bone volume was measured using multidetector computed tomography (MDCT).Findings: G-CSF reduced the density of the head and greater trochanter of femural bone in mice. The IFN-a  alone increased bone density in the greater trochanter and the volume of the trabecular bone. This factor, in combination with G-CSF, strongly enhanced bone density and increased the volume of the trabecular bone.Conclusion: Therefore, administration of IFN-a may inhibit G-CSF-induced bone loss in inflammatory and treatment conditions.

Keywords

References

  1. Clayton ES, Hochberg MC. Osteoporosis and osteoarthritis, rheumatoid arthritis and spondylarthropathies. Curr Osteoporos Rep 2013; 11(4): 257-62.
  2. Sozzani S, Bosisio D, Scarsi M, Tincani A. Type I interferons in systemic autoimmunity. Autoimmunity 2010; 43(3): 196-203.
  3. Barreda DR, Hanington PC, Belosevic M. Regulation of myeloid development and function by colony stimulating factors. Dev Comp Immunol 2004; 28(5): 509-54.
  4. Nakamura H, Ueki Y, Sakito S, Matsumoto K, Yano M, Miyake S, et al. High serum and synovial fluid granulocyte colony stimulating factor (G-CSF) concentrations in patients with rheumatoid arthritis. Clin Exp Rheumatol 2000; 18(6): 713-8.
  5. Lawlor KE, Campbell IK, Metcalf D, O'Donnell K, van Nieuwenhuijze A, Roberts AW, et al. Critical role for granulocyte colony-stimulating factor in inflammatory arthritis. Proc Natl Acad Sci U S A 2004; 101(31): 11398-403.
  6. Eyles JL, Roberts AW, Metcalf D, Wicks IP. Granulocyte colony-stimulating factor and neutrophils--forgotten mediators of inflammatory disease. Nat Clin Pract Rheumatol 2006; 2(9): 500-10.
  7. Cornish AL, Campbell IK, McKenzie BS, Chatfield S, Wicks IP. G-CSF and GM-CSF as therapeutic targets in rheumatoid arthritis. Nat Rev Rheumatol 2009; 5(10): 554-9.
  8. Dale DC. Colony-stimulating factors for the management of neutropenia in cancer patients. Drugs 2002; 62(Suppl 1): 1-15.
  9. Grigg A, Begley CG, Juttner CA, Szer J, To LB, Maher D, et al. Effect of peripheral blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. Bone Marrow Transplant 1993; 11(Suppl 2): 23-9.
  10. Kuwabara H, Wada T, Oda T, Yoshikawa H, Sawada N, Kokai Y, et al. Overexpression of the granulocyte colony-stimulating factor gene impairs bone morphogenetic protein responsiveness in mice. Lab Invest 2001; 81(8): 1133-41.
  11. Takamatsu Y, Simmons PJ, Moore RJ, Morris HA, To LB, Levesque JP. Osteoclast-mediated bone resorption is stimulated during short-term administration of granulocyte colony-stimulating factor but is not responsible for hematopoietic progenitor cell mobilization. Blood 1998; 92(9): 3465-73.
  12. Purton LE, Lee MY, Torok-Storb B. Normal human peripheral blood mononuclear cells mobilized with granulocyte colony-stimulating factor have increased osteoclastogenic potential compared to nonmobilized blood. Blood 1996; 87(5): 1802-8.
  13. Hirbe AC, Uluckan O, Morgan EA, Eagleton MC, Prior JL, Piwnica-Worms D, et al. Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner. Blood 2007; 109(8): 3424-31.
  14. Semerad CL, Christopher MJ, Liu F, Short B, Simmons PJ, Winkler I, et al. G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood 2005; 106(9): 3020-7.
  15. Billiau A. Interferon beta in the cytokine network: an anti-inflammatory pathway. Mult Scler 1995; 1(Suppl 1): S2-S4.
  16. Hoyo-Becerra C, Schlaak JF, Hermann DM. Insights from interferon-alpha-related depression for the pathogenesis of depression associated with inflammation. Brain Behav Immun 2014; 42: 222-31.
  17. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007; 356(22): 2271-81.
  18. Avnet S, Cenni E, Perut F, Granchi D, Brandi ML, Giunti A, et al. Interferon-alpha inhibits in vitro osteoclast differentiation and renal cell carcinoma-induced angiogenesis. Int J Oncol 2007; 30(2): 469-76.
  19. Lari R, Fleetwood AJ, Kitchener PD, Cook AD, Pavasovic D, Hertzog PJ, et al. Macrophage lineage phenotypes and osteoclastogenesis--complexity in the control by GM-CSF and TGF-beta. Bone 2007; 40(2): 323-36.
  20. Nishida N, Komatsu Y, Komeda T, Fukuda Y. Interferon-alpha improves bone resorption and osteopenia in patients with chronic hepatitis C. Hepatol Res 2006; 34(4): 222-7.
  21. Gur A, Dikici B, Nas K, Bosnak M, Haspolat K, Sarac AJ. Bone mineral density and cytokine levels during interferon therapy in children with chronic hepatitis B: does interferon therapy prevent from osteoporosis? BMC Gastroenterol 2005; 5: 30.
  22. Mensah KA, Mathian A, Ma L, Xing L, Ritchlin CT, Schwarz EM. Mediation of nonerosive arthritis in a mouse model of lupus by interferon-alpha-stimulated monocyte differentiation that is nonpermissive of osteoclastogenesis. Arthritis Rheum 2010; 62(4): 1127-37.
  23. Takaishi Y, Ikeo T, Nakajima M, Miki T, Fujita T. A pilot case-control study on the alveolar bone density measurement in risk assessment for bisphosphonate-related osteonecrosis of the jaw. Osteoporos Int 2010; 21(5): 815-25.
  24. Boivin G, Meunier PJ. The degree of mineralization of bone tissue measured by computerized quantitative contact microradiography. Calcif Tissue Int 2002; 70(6): 503-11.
  25. Inoue K, Hamano T, Nango N, Matsui I, Tomida K, Mikami S, et al. Multidetector-row computed tomography is useful to evaluate the therapeutic effects of bisphosphonates in glucocorticoid-induced osteoporosis. J Bone Miner Metab 2014; 32(3): 271-80.
  26. Wang YX, Griffith JF, Zhou H, Choi KC, Hung VW, Yeung DK, et al. Rat lumbar vertebrae bone densitometry using multidetector CT. Eur Radiol 2009; 19(4): 882-90.
  27. Takayanagi H, Sato K, Takaoka A, Taniguchi T. Interplay between interferon and other cytokine systems in bone metabolism. Immunol Rev 2005; 208: 181-93.
  28. Wilkison M, Gauss K, Ran Y, Searles S, Taylor D, Meissner N. Type 1 interferons suppress accelerated osteoclastogenesis and prevent loss of bone mass during systemic inflammatory responses to Pneumocystis lung infection. Am J Pathol 2012; 181(1): 151-62.
  29. Johannesdottir F, Aspelund T, Reeve J, Poole KE, Sigurdsson S, Harris TB, et al. Similarities and differences between sexes in regional loss of cortical and trabecular bone in the mid-femoral neck: the AGES-Reykjavik longitudinal study. J Bone Miner Res 2013; 28(10): 2165-76.
  30. Schwarz EM, Looney RJ, Drissi MH, O'Keefe RJ, Boyce BF, Xing L, et al. Autoimmunity and bone. Ann N Y Acad Sci 2006; 1068: 275-83.
Journal of Isfahan Medical School
Volume 33, Issue 334 - Serial Number 334
March and April 2015
Pages 703-713

Files

History

  • Receive Date: 25 February 2015
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics