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AB0794 Possible Molecular Mechanism of Lactoferrin Action on Bone Formation
  1. P. Sadchikov1,
  2. I. Goldman2,
  3. A. Chernousov2,
  4. E. Sadchikova2
  1. 1Faculty of Fundamental Medicine, Lomonoso Moscow State University
  2. 2Transgenebank, Institute of Gene Biology, Moscow, Russian Federation

Abstract

Background Lactoferrin (LF) is a multifunctional protein, for which several biological activities were determined, among which the main are antimicrobial, antiviral, antifungal, anti-inflammatory and antioxidant effects. LF takes an active part in stimulation of tissue regeneration processes. LF's active role in the stimulation of tissue regeneration processes was established. In the last decade LF has also been shown to play the role in bone formation.

Objectives In experiments carried out in different countries, it was found that the ovariectomized experimental animals, when giving LF per os, achieved relief of symptoms of osteoporosis, occurring at similar postmenstrual osteoporosis in women and human aging. Accumulating facts are showing a decrease in physiological serum LF in patients under pathological conditions of bone formation. In molecular genetic studies the identical mechanisms, resulting in reduced expression of LF and the emergence of bone desorption were determined.

Methods We present a possible model of bone formation under the LF influence (Fig).

Results According to our conception in osteoporosis, various injuries, or surgical impacts associated with the bones, the involvement of LF in the regenerative processes of the bone formation, apparently, is implemented as follows: as a result of damage of different tissues are released risk molecules – alarmins (high-mobility group protein B1 (HMGB1), S100 protein, IL-α, IL-33), which are necessary to repair damaged tissues, including bone. They interact with alarmins receptors on the surface of leukocytes, thus there is a release of proinflammatory cytokines (TNFα, IL-6, IL-1β, IL-8, INFγ) (Fig. Phase I). Further, under the action of IL-8, which is a chemotactic factor for neutrophils in the bone defect area segmented leukocytes migrate from granules which stands LF (Fig. Phase II). Then LF immerses in osteoblasts (OB), activating them, and osteoclasts (OC), inhibiting their activity (Fig. Phase III).

Conclusions According to the presented model, the LF is simultaneously a factor of implementing the calcium transfer. The ability of LF to bind calcium is well known. The transfer of calcium in the bone tissue due to the complex LF-Calmodulin-Ca ++ (Fig.).

It is possible that the expansion of research of the role of LF in bone formation will help create new and effective drugs to combat osteoporosis.

Disclosure of Interest None declared

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