Preview

Osteoporosis and Bone Diseases

Advanced search

THE MOLECULAR MECHANISM OF LACTOFERRIN INFLUENCE ON BONE FORMATION

https://doi.org/10.14341/osteo2016312-22

Abstract

In present critical review of systematized materials on the breakthrough achievements of the last decade - the discovery of the effect of protein lactoferrin (LF) on bone formation. It is shownthat LF increases the number of osteoblasts, stimulate their proliferation and differentiation, and prevents their destruction. Action of LF exceeds that of many other previously established bone-forming factors. LF increases the ability of osteoblasts to synthesize and mineralize bone matrix. Apparently, the effect of LF on bone anabolism ensured by the presence of specific receptors on osteoblasts. It was found that LF also inhibits the formation of osteoclasts. Experimental studies have demonstrated that LF prevents the destruction of bone tissue in ovariectomizedanimals and, thus, developing the type of postmenstrual osteoporosis in women. We get the first clinical studies demonstrating an increase in the period of healing of bone injuries while reducing the level of endogenous LF. Since molecular research establishes that the expression of the LF gene is regulated by estrogen, which reduces the development of postmenopausal osteoporosis (PMO) in women, there is a need to further investigate the relationship of these processes, which will help to create a basis for the management of bone formation.

References

1. Moyer V.A.; US Preventive Services Task Force. Vitamin D and calcium supplementation to prevent fractures in adults: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2013; 158: 691-696.

2. Osteoporosis prevention. http://www.mayoclinic.org/diseases-conditions/osteoporosis/basics/prevention/con-20019924

3. L. Langsetmo, C. Berger, N. Kreiger, C.S. Kovacs, D.A. Hanley D.A., Jamal S.A., Whiting S.J., Genest J., Morin S.N., Hodsman A., Calcium and vitamin D intake and mortality: results from the Canadian Multicentre Osteoporosis Study (CaMos) Clin Endocrinol Metab. 2013 Jul; 98(7): 3010-8. doi: 10.1210/jc.2013-1516. Epub 2013 May 23.

4. Martinez Diaz-Guerra G.1, Jôdar Gimeno E., Reyes Garcia R., Gômez Saez J.M., Munoz-Torres M.; [Normocalcemic primary hyperparathyroidism: recommendations for management and follow-up]. Endocrinol Nutr. 2013 0ct; 60(8): 456.e1-6. doi: 10.1016/j.endonu.2013.01.015. Epub 2013 May 7.

5. Borland S. £16 vitamin D treatment that cost the NHS £2400 due to 'supply problems' http://www.dailymail.co.uk/health/article-2104048/16-vitamin-D-treatment-cost-NHS-2400-supply-problems.html

6. I.R. Reid MD, M.J. Bolland PhD, A. Grey MD Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis // The Lancet - 11 January 2014 ( Vol. 383, Issue 9912, Pages 146-155 ).

7. Lawlor D.A.1, Wills A.K., Fraser A., Sayers A., Fraser W.D., Tobias J.H. Association of maternal vitamin D status during pregnancy with bone-mineral content in offspring: a prospective cohort study. Lancet. 2013 Jun 22; 381(9884): 2176-83. doi: 10.1016/S0140-6736(12)62203-X. Epub 2013 Mar 19.

8. Hill T.R., Granic A., Davies K., Collerton J., Martin-Ruiz C., Siervo M., Mathers J.C., Adamson A.J., Francis R.M., Pearce S.H., Razvi S., Kirkwood T.B., Jagger C. Serum 25-hydroxyvitamin D concentration and its determinants in the very old: the Newcastle 85+ Study. Osteoporos Int. 2016 Mar; 27(3): 1199-208. doi: 10.1007/s00198-015-3366-9. Epub 2015 Oct 14.

9. Wolff I., van Croonenborg J., Kemper H.C.G. et al. The effect of exercise training programs on bone mass: control trails in pre and postmуnopausal women. Osteoporosis Int., 1999, 9: 1-12.

10. S. Iwase, N. Nishimura and T. Mano “Topics in Osteoporosis”, book edited by Margarita Valdes Flores, ISBN 978-953-51-1066-8, Published: May 15, 2013 under CC BY 3.0 license

11. http://archive.today.uci.edu/news/release_detail. asp?key=1864 http://www.dailymail.co.uk/sciencetech/article-1129089/Astronauts-risk-hip-fractures-later-life-space-damages-bone-strength.html http://www.space.com/6354-space-station-astronauts-lose-bone-strength-fast.html

12. Cornish J., Callon K.E., Naot D., Palmano K.P., Banovic T., Bava U., Watson M., Lin J.M., Tong P.C., Chen Q., Chan V.A., Reid H.E., Fazzalari N., Baker H.M., Baker E.N., Haggarty N.W., Grey A.B., Reid I.R. Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo. Endocrinology. 2004 Sep; 145(9): 4366-74. Epub 2004 May 27.

13. Naot D., Grey A., Reid I.R., Cornish J. Lactoferrin-- a novel bone growth factor. Clin Med Res. 2005 May; 3(2): 93-101.

14. Cornish J., Palmano K., Callon K.E., Watson M., Lin J.M., Valenti P., Naot D., Grey A.B., Reid I.R. Lactoferrin and bone; structure-activity relationships. Biochem Cell Biol. 2006 Jun; 84(3): 297-302.

15. H.J. Vogel. Biochemistry Research Group, 233. Biochem. Cell Biol. 90: 233-244 (2012) doi: 10.1139/O2012-01

16. Jan M. Steijns and A. C. M. van Hooijdonk. Occurrence, structure, biochemical properties and technological characteristics of lactoferrin. British Journal of Nutrition 2000, 84, Suppl. 1, S11±S17.

17. Naidu A.S. Lactoferrin: Natural. Multifunctional. Antimicrobial. 2000, Boca Raton: CRC Press LLC.

18. Legrand D., Pierce A., Elass E. et al. J. Lactoferrin structure and functions. Adv. Exp. Med. Biol. 2008; v. 606: p.163-94.

19. Lillis A., Van Duyn L., Murphy-Ullrich J., and Strickland D. The low density lipoprotein receptor-related protein 1: Unique tissue-specific functions revealed by selective gene knockout studies Physiol Rev. 2008 July; 88(3): 887-918.

20. Siao S.C., Li K.J., Hsieh S.C., et.al Tamm-Horsfall glycoprotein enhances PMN phagocytosis by binding to cell surface-expressed lactoferrin and cathepsin G that activates MAP kinase pathway Molecules. 2011 Mar 3; 16(3): 2119-34.

21. Curran C.S., Demick K.P., Mansfield J.M. Lactoferrin activates macrophages via TLR4-dependent and -independent signaling pathways. Cell Immunol. 2006; 242(1): 23-30

22. Oh S.M., Pyo C.W., Kim Y., Choi S.Y. Neutrophil lactoferrin upregulates the human p53 gene through induction of NF-kappaB activation cascade. Oncogene. 2004; 23(50): 8282-9.

23. Wlodarski K. Lactoferrin--a promising bone-growth promoting milk-derived glycoprotein. Chir Narzadow Ruchu Ortop Pol. 2009 Sep-Oct; 74(5): 257-9,322-3.

24. Ieni A., Barresi V., Grosso M. and Tuccari G. Immunohistochemical evidence of lactoferrin in human embryo-fetal bone and cartilage tissues Cell Biol Int. 2010 Aug; 34(8): 845-9. doi: 10.1042/CBI20090358].

25. Cornish J., Naot D. Lactoferrin as an effector molecule in the skeleton Biometals. 2010 Jun; 23(3): 425-30. doi: 10.1007/ s10534-010-9320-6. Epub 2010 Mar.

26. Chan J.K., Roth J., Oppenheim J.J, Alarmins: awaiting a clinical response J Clin Invest. 2012 August 1; 122(8): 2711-2719.

27. Gifford J.L., Ishida H., Vogel H.J. Structural characterization of the interaction of human lactoferrin with calmodulin. PLoS One. 2012; 7(12): e51026.

28. Hou J.M.1, Xue Y., Lin Q.M. Bovine lactoferrin improves bone mass and microstructure in ovariectomized rats via OPG/RANKL/RANK pathway. Acta Pharmacol Sin. 2012 Oct; 33(10): 1277-84. doi: 10.1038/aps.2012.83. Epub 2012 Aug 20.

29. Du M.1, Xu W., Yi H., Han X., Wang C., Zhang L. Protective effects of bovine colostrum acid proteins on bone loss of ovariectomized rats and the ingredients identification. Mol Nutr Food Res. 2011 Feb; 55(2): 220-8. doi: 10.1002/mnfr.200900593.

30. Guo H.Y.1, Jiang L., Ibrahim S.A., Zhang L., Zhang H., Zhang M., Ren F.Z. Orally administered lactoferrin preserves bone mass and microarchitecture in ovariectomized rats. J Nutr. 2009 May; 139(5): 958-64. doi: 10.3945/jn.108.100586. Epub 2009 Mar 25.

31. Malet A.1, Bournaud E., Lan A., Mikogami T., Tomé D., Blais A. Bovine lactoferrin improves bone status of ovariecto-mized mice via immune function modulation. Bone. 2011 May 1; 48(5): 1028-35. doi: 10.1016/j.bone.2011.02.002. Epub 2011 Feb 16.

32. Cornish J., Callon K., King A., Edgar S., Reid I.R. The effect of leukemia inhibitory factor on bone in vivo. Endocrinology 1993, 132: 1359-1366.

33. Bharadwaj S., Naidu A.G., Betageri G.V., Prasadarao N.V., Naidu A.S. Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women Osteoporos Int. 2009 Sep; 20(9): 1603-11.

34. Bharadwaj S., Naidu T.A., Betageri G.V., Prasadarao N.V., Naidu A.S. Inflammatory responses improve with milk ribonuclease-enriched lactoferrin supplementation in postmenopausal women. Inflamm. Res. Inflamm Res. 2010 Nov; 59(11): 971-8.

35. Kang, J.F., Li, X.L., Zhou, R.Y., Li, L.H., Feng, F.J., and Guo, X.L. Bioinformatics analysis of lactoferrin gene for several species. Biochem Genet 2008, 46, 312-322.

36. Shi H., Shigeta H., Yang N., Fu K., O'Brian G., and Teng C.T. Human estrogen receptor-like 1 (ESRL1) gene: genomic organization, chromosomal localization, and promoter characterization. Genomics 1997, 44, 52-60.

37. Teng, C.T., Liu, Y, Yang, N., Walmer, D., and Panella, T. Differential molecular mechanism of the estrogen action that regulates lactoferrin gene in human and mouse. Mol Endocrinol 1992, 6, 1969-1981.

38. Yang, N., Shigeta, H., Shi, H., and Teng, C. T. Estrogen-related receptor, hERR1, modulates estrogen receptor-mediated response of human lactoferrin gene promoter. J Biol Chem, 1996: 271, 5795-5804.

39. Wang, L.H., Tsai, S.Y., Cook, R.G., Beattie, W.G., Tsai, M.J., and O'Malley, B.W. COUP transcription factor is a member of the steroid receptor superfamily. Nature; 1989, 340, 163-166.

40. Teng, C.T., Gladwell, W., Beard, C., Walmer, D., Teng, C.S., and Brenner, R. Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium. Mol Hum Reprod; 2002, 8, 58-67 6.

41. Cooney, A.J., Lee, C.T., Lin, S.C., Tsai, S.Y., and Tsai, M.J. Physiological function of the orphans GCNF and COUP-TF. Trends Endocrinol Metab, 2001 12, 247-251.

42. Sugiyama, T., Wang, J.C., Scott, D.K., and Granner, D.K. Transcription activation by the orphan nuclear receptor, chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI). Definition of the domain involved in the glucocorticoid response of the phosphoenolpyruvate carboxykinase gene. J Biol Chem; 2000 275, 3446-3454.

43. Rossouw J.E.1, Anderson G.L., Prentice R.L., LaCroix A.Z., Kooperberg C., Stefanick M.L., Jackson R.D., Beresford S.A., Howard B.V., Johnson K.C., Kotchen J.M., Ockene J. Risks and benefits of estrogen + progestin in healthy posmenopausal women: principal results From the Women's Health Initiative randomized controlled trial.//JAMA,2002, 288: 321-333.

44. Khanna-Gupta, A., Zibello, T., Simkevich, C., Rosmarin, A.G., and Berliner, N. Sp1 and C/EBP are necessary to activate the lactoferrin gene promoter during myeloid differentiation. Blood; 2000 95, 3734-3741. 10.

45. Darlington, G.J., Ross, S.E., and MacDougald, O.A. The role of C/EBP genes in adipocyte differentiation. J Biol Chem; 1998 273, 30057-30060.

46. Nerlov, C. C/EBPs: recipients of extracellular signals through proteome modulation. Curr Opin Cell Biol 20, 180-185; Takiguchi, M. (1998). The C/EBP family of transcription factors in the liver and other organs. Int J Exp Pathol; 2008 79, 369-391.

47. Khanna-Gupta, A., Zibello, T., Sun, H., Gaines, P, and Berliner, N. Chromatin immunoprecipitation (ChIP) studies indicate a role for CCAAT enhancer binding proteins alpha and epsilon (C/EBP alpha and C/EBP epsilon) and CDP/cut in myeloid maturation-induced lactoferrin gene expression. Blood 2003, 101, 3460-3468.

48. Khanna-Gupta, A., Zibello, T., Sun, H., Lekstrom-Himes, J., and Berliner, N. C/EBP epsilon mediates myeloid differentiation and is regulated by the CCAAT displacement protein (CDP/ cut). Proc Natl Acad Sci; 2001 USA 98, 8000-8005.

49. Lee, M.O., Liu, Y., and Zhang, X.K. A retinoic acid response element that overlaps an estrogen response element mediates multihormonal sensitivity in transcriptional activation of the lactoferrin gene. Mol Cell Biol; 1995 15, 4194-4207.

50. Shi, H., and Teng, C. Promoter-specific activation of mouse lactoferrin gene by epidermal growth factor involves two adjacent regulatory elements. Mol Endocrinol; 1996 10, 732-741; 16.

51. Shi, H., and Teng, C.T. Characterization of a mitogen-response unit in the mouse lactoferrin gene promoter. J Biol Chem; 1994, 269, 12973-12980.

52. Teng, C., Shi, H., Yang, N., and Shigeta, H. Mouse lactoferrin gene. Promoter-specific regulation by EGF and cDNA cloning of the EGF-response-element binding protein. Adv Exp Med Biol; 1998 443, 65-78.

53. Li, Y., Limmon, G.V., Imani, F., and Teng, C. Induction of lactoferrin gene expression by innate immune stimuli in mouse mammary epithelial HC-11 cells. Biochimie. 2009 Jan; 91(1): 58-67.

54. Firth, M.A., Shewen, P.E., and Hodgins, D. C. Passive and active components of neonatal innate immune defenses. Anim Health Res Rev; 2005, 6, 143-158. 20.

55. Zheng, J., Ather, J.L., Sonstegard, T.S., and Kerr, D.E. Characterization of the infection-responsive bovine lactoferrin promoter. Gene; 2005 353, 107-117.

56. Liu, D., Wang, X., Zhang, Z., and Teng, C.T. An intronic alternative promoter of the human lactoferrin gene is activated by Ets. Biochem Biophys Res Commun; 2003, 301, 472-479.

57. Siebert, P.D., and Huang, B. C. (1997). Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines. Proc Natl Acad Sci USA; 1997,94, 2198-2203.

58. Goldberg, G.S., Kunimoto, T., Alexander, D.B., Suenaga, K., Ishidate, F., Miyamoto, K., Ushijima, T., Teng, C.T., Yokota, J., Ohta, T., and Tsuda, H. Full length and delta lactoferrin display differential cell localization dynamics, but do not act as tumor markers or significantly affect the expression of other genes. Med Chem; 2005, 1, 57-64. 24.

59. Liu, D., Wang, X., Zhang, Z., and Teng, C.T. An intronic alternative promoter of the human lactoferrin gene is activated by Ets. Biochem Biophys Res Commun; 2003, 301, 472-479.

60. Mariller, C., Benaissa, M., Hardiville, S., Breton, M., Pradelle, G., Mazurier, J., and Pierce, A. (2007). Human delta-lactoferrin is a transcription factor that enhances Skp1 (S-phase kinase-associated protein) gene expression. FEBS J; 2007, 274, 2038-2053.

61. Mariller, C., Hardiville, S., Hoedt, E., Benaissa, M., Mazurier, J., and Pierce, A. Proteomic approach to the identification of novel delta-lactoferrin target genes: Characterization of DcpS, an mRNA scavenger decapping enzyme. Biochimie, 2009 Jan; 91(1 ): 109-22.

62. Breton, M., Mariller, C., Benaissa, M., Caillaux, K., Browaeys, E., Masson, M., Vilain, J.P., Mazurier, J., and Pierce, A. Expression of delta-lactoferrin induces cell cycle arrest. Biometals; 2004, 17, 325-329. 28.

63. Ishikado A.1, Imanaka H., Takeuchi T., Harada E., Makino T. Liposomalization of lactoferrin enhanced it’s antiinflammato ry effects via oral administration. Biol Pharm Bull. 2005 Sep; 28(9): 1717-21.

64. Inubushi T., Kawazoe A., Miyauchi M., Kudo Y., Ao M., Ishikado A., Makino T., Takata T. Molecular mechanisms of the inhibitory effects of bovine lactoferrin on lipopolysaccharidemediated osteoclastogenesis. J Biol Chem. 2012 Jul 6; 287(28): 23527-36. doi: 10.1074/jbc.M111.324673. Epub 2012 May 16


Review

For citations:


Sadchikov P.E., Goldman I.L., Razin S.V., Chernousov A.D., Alekseeva L.I., Sadchikova E.R. THE MOLECULAR MECHANISM OF LACTOFERRIN INFLUENCE ON BONE FORMATION. Osteoporosis and Bone Diseases. 2016;19(3):12-22. (In Russ.) https://doi.org/10.14341/osteo2016312-22

Views: 3909


ISSN 2072-2680 (Print)
ISSN 2311-0716 (Online)