lactoferrin and Osteoporosis

Lactoferrin is an iron-binding protein secreted by mammary gland, thus present in milk and in colostrum, which are a cheap and easy to obtain sources of this protein. Lactoferrin is also present in specific granules of neutrophils. Lactoferrin is a multifunctional agent involved, among others in the immune response and in the regulation of bone metabolism. Lactoferrin actives of osteoblast proliferation and bone matrix secretion, and inhibits apoptosis of osteoblast and osteoclastogenesis. Lactoferrin administered to rodents accelerates bone healing and prevents bone loss induced by ovariectomy. Therefore the use of lactoferrin or milk whey in osteoporosis treatment and prevention is postulated.

Topics: Animals; Apoptosis; Bone Regeneration; Cell Proliferation; Female; Humans; Lactoferrin; Osteoblasts; Osteoporosis; Ovariectomy; Wound Healing

Osteoporosis can be classified as an inflammatory disease and the crosstalk between the immune system and bone growth should be considered. The effects of bovine lactoferrin on bone by osteoimmunology were investigated in the present study. Ten week old female BALB/c mice were ovariectomized (OVX) and fed for 12 weeks with a control diet or lactoferrin (2, 20 and 100 mg kg-1 d-1). The results showed that following 12 weeks of treatment after surgery, OVX resulted in bone loss, but treatment with lactoferrin preserved bone homeostasis. Lactoferrin significantly improved bone mineral density, and increased the serum levels of alkaline phosphatase, while it decreased the serum levels of tartrate-resistant acid phosphatase. Furthermore, according to micro-computed tomography (micro-CT), the bone volume per tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N) were elevated. The results indicated that the structure model index (SMI) was reduced in the OVX + LF groups. Additionally, lactoferrin enhanced the Max-Load and Max-Stress values of the femur, and increased the content of Ca and P. However, lactoferrin suppressed the RANKL/OPG ratio in OVX mice. Moreover, interferon-γ, interleukin-5 and interleukin-10 were elevated significantly in the OVX + LF groups. Lactoferrin had a positive effect on the bone micro-environment and might be a pleiotropic protein for the prevention and treatment of estrogen-dependent bone loss via the osteoimmunology pathway.

Topics: Animals; Bone and Bones; Bone Density; Cattle; Female; Homeostasis; Humans; Interferon-gamma; Interleukin-5; Lactoferrin; Mice; Mice, Inbred BALB C; Osteoporosis; Ovariectomy; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B

Lactoferrin (LF), an 80-kDa iron-binding glycoprotein, is a pleiotropic factor found in colostrum, milk, saliva and epithelial cells of the exocrine glands. The aim of this study was to evaluate the effects of LF on the bones in ovariectomized (Ovx) rats and to identify the pathways that mediate the anabolic action of LF on the bones.. Female Sprague-Dawley rats (6-month-old) underwent ovariectomy, and were treated with different doses of LF (10, 100, 1000, and 2000 mg·kg(-1)·d(-1), po) or with 7β-estradiol (0.1 mg·kg(-1), im, each week) as the positive control. By the end of 6 month-treatments, the bone mass and microstructure in the rats were scanned by micro-computed tomography (micro-CT), and the bone metabolism was evaluated with specific markers, and the mRNA levels of osteoprotegerin (OPG) and the receptor-activator of nuclear factor κB ligand (RANKL) in femur were measured using qRT-PCR.. LF treatment dose-dependently elevated the bone volume (BV/TV), trabecular thickness (TbTh) and trabecular number (TbN), and reduced the trabecular separation (TbSp) in Ovx rats. Furthermore, higher doses of LF (1000 and 2000 mg·kg(-1)·d(-1)) significantly increased the bone mineral density (BMD) compared with the untreated Ovx rats. The higher doses of LF also significantly increased the serum levels of OC and BALP, and decreased the serum levels of β-CTx and NTX. LF treatment significantly increased the OPG mRNA levels, and suppressed the RANKL mRNA levels, and the RANKL/OPG mRNA ratio in Ovx rats.. Oral administration of LF preserves the bone mass and improves the bone microarchitecture. LF enhances bone formation, reduces bone resorption, and decreases bone mass loss, possibly through the regulation of OPG/RANKL/RANK pathway.

Topics: Analysis of Variance; Animals; Bone and Bones; Bone Density; Bone Density Conservation Agents; Female; Femur; Lactoferrin; Lumbar Vertebrae; Metabolic Networks and Pathways; Organ Size; Osteoporosis; Osteoprotegerin; Ovariectomy; RANK Ligand; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Receptor Activator of Nuclear Factor-kappa B; X-Ray Microtomography

At the whole organ level, degenerative mechanisms in bone and cartilage are primarily attributed to modifications in loading pattern. Either a change in magnitude or location can initiate a degenerative path. At the micro scale we often see changes in structure such as porosity increase in bone and fibrillation in cartilage. These changes contribute to a reduced structural integrity that weakens the bulk strength of tissue. Finally, at the cell level we have modeling and remodeling pathways that may be disrupted through disease, drugs and altered stimulus from the micro and macro scales. In order to understand this entire process and the roles each level plays a multiscale modeling framework is necessary. This framework can take whole body loadings and pass information through finer spatial scales in order to understand how everyday dynamic movements influence micro and cellular response. In a similar manner, cellular and microstructural processes regulate whole bulk properties and modify whole organ strength. In this study we highlight the multiscale links developed as part of the open-source ontologies for the Physiome Project using the lower limb as an example. We consider the influence of remodeling in (i) anabolic treatments in cortical bone; and (ii) subchondral bone and cartilage degeneration.

Topics: Aged; Anterior Cruciate Ligament; Anthropometry; Bone and Bones; Bone Remodeling; Bone Resorption; Cartilage, Articular; Computer Simulation; Gait; Humans; Imaging, Three-Dimensional; Inflammation; Lactoferrin; Magnetic Resonance Imaging; Models, Anatomic; Models, Biological; Osteoarthritis; Osteoporosis; Porosity