Lactoferrin as an effector molecule in the skeleton.

Lactoferrin is a pleiotropic factor with potent antimicrobial and immunomodulatory activities. In recent years, studies have shown that lactoferrin also acts on the skeleton to promote bone growth. Lactoferrin stimulates the proliferation and differentiation of the bone forming cells, the osteoblasts, and acts as a survival factor for these cells. Lactoferrin also inhibits osteoclastogenesis, reducing the number of cells that can actively resorb bone, thus producing a greater overall increase in bone volume. In vivo, local injection of lactoferrin results in substantial increases in bone area, establishing lactoferrin as an effector molecule in the skeleton. Investigations of the mechanism of action of lactoferrin in bone cells showed that the mitogenic effect of lactoferrin in osteoblasts is mediated mainly through LRP1, a member of the low density lipoprotein receptor-related proteins. Lactoferrin induces activation of p42/44 MAPK signaling as well as PI3-kinase-dependent phosphorylation of Akt in osteoblasts. Differential gene expression studies indicated a possible role for the activation of IGF1, Ptgs2 and Nfatc1 in mediating the mitogenic activity of lactoferrin in osteoblasts. Lactoferrin is a positive regulator of bone with a possible physiological role in bone growth and healing. There is a growing interest in the potential use of lactoferrin for the improvement of bone health, and in a number of recent studies dietary lactoferrin supplementation improved bone mineral density and bone strength. Lactoferrin appears to be a promising candidate for the development of an anabolic therapeutic factor for osteoporosis.