title: Bovine lactoferrin improves bone status of ovariectomized mice via immune function modulation.
abstract: We have previously shown that bovine lactoferrin (bLF) supplementation can have a beneficial effect on postmenopausal bone loss by modulating bone formation and resorption. A direct effect of bLF on bone metabolism is support by its presence in mice blood. Moreover we know that LF plays a key role in innate immunity and recent studies have shown its ability to modulate adaptive immunity. In particular bLF ingestion prevents recruitment and activation of immune cells at inflammatory sites. We propose that LF through its ability to modulate maturation and differentiation of leucocytes can participate to abolish the deregulation induced by estrogen deficiency on T cells. This study evaluated the effects of bovine lactoferrin on immune function in ovariectomized mice. We investigated whether bLF ingestion could prevent bone loss via modulation of immune function. Three-month-old female C3H mice were either ovariectomized or sham-operated and fed for 1, 2 or 4 months with a control diet (AIN-93M) or the same diet including 10g bLF/kg diet. Bone mineral density was determined using a Lunar Piximus densitometer. The immune parameters were assessed by flow cytometry. In addition, Real-Time PCR was performed to quantify TNFα expression and plasma cytokines were measured at 4 months with Luminex. Ovariectomy induced significant changes on bone parameters and increased recruitment of macrophages, dendritic cells, and B and T cells associated with T lymphocyte activation in bone marrow. Compared to the control diet, ingestion of bLF-enriched diet for 2 months prevented T cell activation and restored dendritic and B cell populations in the bone micro-environment in ovariectomized mice. Furthermore, TNFα expression in bone was decreased by bLF supplementation after 2 and 4 months. Similarly, a decreased plasma level of TNFα was observed concomitantly to an increase of IL-10 level. In conclusion, these experiments suggest that bLF can mediate the prevention of lymphocyte activation and cytokine release in the bone micro-environment. Dietary bLF supplementation could have a beneficial effect on postmenopausal bone loss by modulating immune function.
authors.affiliation: AgroParisTech, UMR914 Nutrition Physiology and Ingestive Behavior, Paris, France. arnaud.malet@agroparistech.fr
authors.forename: Arnaud
authors.initials: A
authors.lastname: Malet
authors.forename: Elsa
authors.initials: E
authors.lastname: Bournaud
authors.forename: Annaïg
authors.initials: A
authors.lastname: Lan
authors.forename: Takashi
authors.initials: T
authors.lastname: Mikogami
authors.forename: Daniel
authors.initials: D
authors.lastname: Tomé
authors.forename: Anne
authors.initials: A
authors.lastname: Blais
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000276:immunology*; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D007781:Lactoferrin / Q000008:administration & dosage / Q000494:pharmacology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010052:Ovariectomy; D053245:RANK Ligand / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood / Q000235:genetics
chemical_list: D015415:Biomarkers; D053245:RANK Ligand; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007781:Lactoferrin