This Article Full Text Full Text (PDF) All Versions of this Article: 145/9/4366    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cornish, J. Articles by Reid, I. R. Search for Related Content PubMed PubMed Citation Articles by Cornish, J. Articles by Reid, I. R.

Lactoferrin Is a Potent Regulator of Bone Cell Activity and Increases Bone Formation in Vivo

Department of Medicine (J.C., K.E.C., D.N., T.B., U.B., M.W., J.-M.L., P.C.T., Q.C., V.A.C., H.E.R., A.B.G., I.R.R.) and School of Biological Sciences (H.M.B., E.N.B.), University of Auckland, Auckland 1001, New Zealand; Fonterra Research Centre (K.P.P., N.W.H.), Palmerston North 5315, New Zealand; and Institute of Medical and Veterinary Science (N.F.), Adelaide 5000, Australia

Address all correspondence and requests for reprints to: Dr. J. Cornish, Department of Medicine, University of Auckland, Private Bag 92019, Auckland 1001, New Zealand. E-mail: j.cornish{at}auckland.ac.nz.

Lactoferrin is an iron-binding glycoprotein present in epithelial secretions, such as milk, and in the secondary granules of neutrophils. We found it to be present in fractions of milk protein that stimulated osteoblast growth, so we assessed its effects on bone cell function. Lactoferrin produced large, dose-related increases in thymidine incorporation in primary or cell line cultures of human or rat osteoblast-like cells, at physiological concentrations (1–100 µg/ml). Maximal stimulation was 5-fold above control. Lactoferrin also increased osteoblast differentiation and reduced osteoblast apoptosis by up to 50–70%. Similarly, lactoferrin stimulated proliferation of primary chondrocytes. Purified, recombinant, human, or bovine lactoferrins had similar potencies. In mouse bone marrow cultures, osteoclastogenesis was dose-dependently decreased and was completely arrested by lactoferrin, 100 µg/ml, associated with decreased expression of receptor activator of nuclear factor-B ligand. In contrast, lactoferrin had no effect on bone resorption by isolated mature osteoclasts. Lactoferrin was administered over calvariae of adult mice for 5 d. New bone formation, assessed using fluorochrome labels, was increased 4-fold by a 4-mg dose of lactoferrin. Thus, lactoferrin has powerful anabolic, differentiating, and antiapoptotic effects on osteoblasts and inhibits osteoclastogenesis. Lactoferrin is a potential therapeutic target in bone disorders such as osteoporosis and is possibly an important physiological regulator of bone growth.

This article has been cited by other articles:

				J. Cornish, A. MacGibbon, J.-M. Lin, M. Watson, K. E. Callon, P. C. Tong, J. E. Dunford, Y. van der Does, G. A. Williams, A. B. Grey, et al. Modulation of Osteoclastogenesis by Fatty Acids Endocrinology, November 1, 2008; 149(11): 5688 - 5695. [Abstract] [Full Text] [PDF]

				G. W. Krissansen Emerging Health Properties of Whey Proteins and Their Clinical Implications J. Am. Coll. Nutr., December 1, 2007; 26(6): 713S - 723S. [Abstract] [Full Text] [PDF]

				J. Cornish, K. E. Callon, U. Bava, M. Watson, X. Xu, J. M. Lin, V. A. Chan, A. B. Grey, D. Naot, C. M. Buchanan, et al. Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E117 - E122. [Abstract] [Full Text] [PDF]

				R A Stein and D P McDonnell Estrogen-related receptor {alpha} as a therapeutic target in cancer Endocr. Relat. Cancer, December 1, 2006; 13(Supplement_1): S25 - S32. [Abstract] [Full Text] [PDF]

				D. Naot, A. Grey, I. R Reid, and J. Cornish Lactoferrin - A Novel Bone Growth Factor Clin. Med. Res., May 1, 2005; 3(2): 93 - 101. [Abstract] [Full Text] [PDF]

				E. Bonnelye and J. E. Aubin Estrogen Receptor-Related Receptor {alpha}: A Mediator of Estrogen Response in Bone J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 3115 - 3121. [Abstract] [Full Text] [PDF]

				A. Grey, T. Banovic, Q. Zhu, M. Watson, K. Callon, K. Palmano, J. Ross, D. Naot, I. R. Reid, and J. Cornish The Low-Density Lipoprotein Receptor-Related Protein 1 Is a Mitogenic Receptor for Lactoferrin in Osteoblastic Cells Mol. Endocrinol., September 1, 2004; 18(9): 2268 - 2278. [Abstract] [Full Text] [PDF]