Lactoferrin and bone: an overview of recent progress

Lactoferrin is an iron-binding glycoprotein that belongs to the transferrin family and is present in milk, other exocrine secretions, and in the circulation. We have shown that lactoferrin, at physiological concentrations, stimulates the mitogenesis, differentiation and survival of the bone-forming cells, osteoblasts, in vitro. In addition, the local injection of lactoferrin in mice calvaria increases new bone formation in vivo. We have demonstrated that the mitogenic effects of lactoferrin in osteoblast-like cells are mediated through LRP1, a member of the LDL receptor-related family (LRP) of proteins and signals through MAP kinase. Lactoferrin is seen to be endocytosed by primary rat osteoblasts, using confocal laser scanning microscopy. Studies using I-125-lactoferrin demonstrate that lactoferrin binds specifically to osteoblastic cells. However, the signalling and endocytic functions of LRP1 are independent of each other, since lactoferrin can activate mitogenic signalling in conditions in which endocytosis is inhibited. In addition to its anabolic effects, lactoferrin dose-dependently decreases the formation of the bone-resorbing cells (osteoclasts). We conclude that lactoferrin has powerful anabolic, differentiating and anti-apoptotic effects on osteoblasts, and inhibits osteoclastogenesis. Lactoferrin may have a potential use as a nutriceutical ingredient in the prevention of osteoporosis.