Lactoferrin is an iron binding glycoprotein which is found at high concentrations in breast milk and other exocrine secretions in the body. In a healthy individual, normal serum levels ranges between 2 and 7 ug/ml but concentrations may be higher during inflammation and sepsis (Cornish et al., 2004). Lactoferrin has the ability to retain iron over a wide pH range, thus involved in iron homeostasis and acts as a pleiotropic factor (Amini & Nair, 2011).
All vertebrate species possess an iron-withholding defence system that scavenges and sequester excess iron in the body. Toxic levels of this metal suppress leukocyte defence mechanisms and stimulate growth of microbial and neoplastic cell invaders. Lactoferrin has both bacteriostatic and bacteriocidal activities. With its iron chelating abilities, it is a key player in the defence system. As a major constituent of leukocyte granules, lactoferrin is released by leukocytes at septic areas and deprives the environment of free iron, ...view middle of the document...
, 2011). It stimulates proliferation and differentiation of osteoblasts (Cornish & Naot, 2010). In studies assessing osteoblast proliferation, lactoferrin produced a dose-related increase in thymidine incorporation in rat-osteoblast-like cells. There was also a significant increase in number of nodules and area of mineralized bone formed, reflecting osteoblast differentiation, at lactoferrin concentrations of 100ug/ml and greater (Cornish et al., 2004). In vivo, local injections of lactoferrin increased mineral apposition rate as well as bone formation rate. There was a significant increase in bone area formed in calvaria of animals treated with lactoferrin, as shown in Figure 5.
Figure 5: Photomicrographs of animal calvaria treated with A) lactoferrin solution and B) vehicle for 5 days. Fluorochrome labels: green = calcein, red = alizarin. Arrow marks the increase in bone growth. Reproduced with permission from Cornish et. al. 2004..
Although the molecular mechanisms of lactoferrin are mostly unknown, a study (Grey et al., 2004) has demonstrated that the low-density lipoprotein receptor-related protein 1 (LRP1), a multiligand member of the LRP family of endocytic receptors, is expressed in osteoblastic cells alongside LRP2 and is partially responsible for the mitogenic effects in osteoblasts by lactoferrin. Not only does lactoferrin stimulates osteoblast proliferation and differentiation, it promotes osteoblast survival. In serum deprivation cultures, it was found to decrease osteoblast apoptosis by up to 70%. In fact, lactoferrin has a profound effect on both osteoblast proliferation and survival when compared to other growth factors including TGF-β, with a 3 to 5 fold increase in rates instead of 20-30% (Cornish et al., 2004).
In addition to its anti-apoptotic actions, lactoferrin inhibits osteoclastogenesis (Amini & Nair, 2011), thereby inhibiting bone resorption. Although lactoferrin reduces osteoclast formation, it does not have effect on the activity of mature osteoclasts.
(Cornish & Naot, 2010) reported that lactoferrin acts as a growth factor in bone tissue when present in physiological concentrations. By injecting lactoferrin locally over the hemicalvaria of adult mice, there was a significant increase in bone area, bone formation rate and mineral apposition rate.