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.

Lactoferrin increases 172ThrAMPK phosphorylation and insulin-induced p473SerAKT while impairing adipocyte differentiation

“…17,18 In primary osteoblasts, lactoferrin stimulated proliferation and differentiation and even acted as a survival factor, thereby, inhibiting apoptosis induced by serum withdrawal and also inhibiting osteoclastogenesis in a murine bone marrow culture. 19 To the best of our knowledge, effects of lactoferrin on the response to insulin (through p473Ser AKT) have never been explored. We aimed to investigate the effects of different lactoferrin concentrations on insulin-induced 473Ser AKT phosphorylation in human hepatocarcinoma (HepG2) and 3T3-L1 fibroblast mouse cell lines.…”

Recombinant human lactoferrin expressed in glycoengineered Pichia pastoris: effect of terminal N-acetylneuraminic acid on in vitro secondary humoral immune response

“…The low-density lipoprotein receptor-related protein-1 and -2 (LRP1 and LRP2) are considered primary LF receptors. Although members of the LRP family are generally considered as endocytic receptors, LRP1 can also function as a signaling receptor [29]. The key to understanding the molecular basis of LF various activities is thought to reside in part according to patterns of glycosylation [37].…”

Effect of Bovine Lactoferrin on Extracellular Matrix Calcification by Human Osteoblast-Like Cells

“…3) Recent studies at the cellular level have demonstrated that lactoferrin promoted the growth of bone-forming osteoblasts and inhibited their apoptosis, suggesting that lactoferrin acted as an osteogenic cytokine. 4) Lactoferrin also inhibits the osteoclastic differentiation and bone resorbing activities. Those beneficial effects of lactoferrin implicate its usefulness as a therapeutic agent in bone tissue regeneration.…”