title: Lactoferrin--a novel bone growth factor.
abstract: Lactoferrin is an iron-binding glycoprotein that belongs to the transferrin family. It is present in breast milk, in epithelial secretions, and in the secondary granules of neutrophils. In healthy subjects lactoferrin circulates at concentrations of 2-7 x 10(-6) g/ml. Lactoferrin is a pleiotropic factor with potent antimicrobial and immunomodulatory activities. Recently, we have shown that lactoferrin can also promote bone growth. At physiological concentrations, lactoferrin potently stimulates the proliferation and differentiation of primary osteoblasts and also acts as a survival factor inhibiting apoptosis induced by serum withdrawal. Lactoferrin also affects osteoclast formation and, in murine bone marrow culture, lactoferrin potently inhibits osteoclastogenesis. In vivo, local injection of lactoferrin above the hemicalvaria of adult mice results in substantial increases in the dynamic histomorphometric indices of bone formation and bone area. The mitogenic effect of lactoferrin in osteoblast-like cells is mediated mainly through LRP1, a member of the family of low-density lipoprotein receptor-related proteins that are primarily known as endocytic receptors. Using confocal laser scanning microscopy, we demonstrated that fluorescently labeled lactoferrin is endocytosed and can be visualized in the cytoplasm of primary osteoblastic cells. Lactoferrin also induces activation of p42/44 MAPK signaling in primary osteoblasts, but the two pathways seem to operate independently as activation of MAPK signaling, but not endocytosis, is necessary for the mitogenic effect of lactoferrin. We conclude that lactoferrin may have a physiological role in bone growth and healing, and a potential therapeutic role as an anabolic factor in osteoporosis.
authors: Department of Medicine, University of Auckland, Auckland, New Zealand. d.naot@auckland.ac.nz
authors: Dorit
authors: D
authors: Naot
authors: Andrew
authors: A
authors: Grey
authors: Ian R
authors: IR
authors: Reid
authors: Jillian
authors: J
authors: Cornish
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004705:Endocytosis; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007335:Insulin-Like Growth Factor II; D026502:LDL-Receptor Related Proteins / Q000502:physiology; D007781:Lactoferrin / Q000494:pharmacology / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D011506:Proteins / Q000494:pharmacology / Q000502:physiology*; D051381:Rats
chemical_list: C035170:IGF2 protein, human; D026502:LDL-Receptor Related Proteins; D011506:Proteins; D007335:Insulin-Like Growth Factor II; D007781:Lactoferrin