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@article{Li:2018:jn/nxy097,
author = {Li, Y and Wang, J and Ren, F and Zhang, W and Zhang, H and Zhao, L and Zhang, M and Cui, W and Wang, X and Guo, H},
doi = {jn/nxy097},
journal = {JOURNAL OF NUTRITION},
pages = {1285--1292},
title = {Lactoferrin Promotes Osteogenesis through TGF-ss Receptor II Binding in Osteoblasts and Activation of Canonical TGF-ss Signaling in MC3T3-E1 Cells and C57BL/6J Mice},
url = {http://dx.doi.org/10.1093/jn/nxy097},
volume = {148},
year = {2018}
}

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TY  - JOUR
AB  - BackgroundLactoferrin (LF), as a major functional protein in dairy products, is known to modulate bone anabolic effects. However, the underlying molecular mechanisms remain unclear; the receptor of LF in osteoblast differentiation has not been identified.ObjectiveThe aims of the study were to 1) illuminate whether the receptor of LF in osteoblast differentiation is transforming growth factor-β (TGF-β) receptor (TβR) II and 2) determine whether the TGF-β signaling pathway is activated by LF in promoting osteogenesis in vitro and in vivo, in addition to P38 and extracellular signal-regulated kinase (ERK) pathways.MethodsWe utilized co-immunoprecipitation to detect any binding of LF to TβRII. Subsequently, the role of the TGF-β signaling pathway involved in LF-induced osteoblast proliferation and differentiation was determined by inhibition of TβRI activity by inhibition and knockout of TβRII expression by small guide RNA (sgRNAs) in MC3T3-E1 cells. In addition, 4-wk-old male C57BL/6J mice were orally administered 100 mg LF/kg body weight for 16 wk, after which any activation of the TGF-β signaling pathway in vivo was measured by Western blots.ResultsLF was shown to directly interact with the TβRII protein and to activate the TGF-β signaling pathway in MC3T3-E1 cells. Inhibition of TβRI activity and knockout TβRII expression both attenuated the stimulation of LF in osteoblast proliferation and differentiation by 30–50%. LF-induced activation of TGF-β canonical signaling resulted in upregulation of osteogenic factors. Moreover, the expression of phosphorylated-drosophila mothers against decapentaplegic protein 2 (SMAD2) was increased by 1-fold after LF treatment in the femoral tissue of mice.ConclusionsThis study provides evidence identifying TβRII as an LF receptor in LF-induced osteoblast differentiation. In addition, the TβRII-dependent TGF-β canonical signaling pathways were p
AU  - Li,Y
AU  - Wang,J
AU  - Ren,F
AU  - Zhang,W
AU  - Zhang,H
AU  - Zhao,L
AU  - Zhang,M
AU  - Cui,W
AU  - Wang,X
AU  - Guo,H
DO  - jn/nxy097
EP  - 1292
PY  - 2018///
SN  - 0022-3166
SP  - 1285
TI  - Lactoferrin Promotes Osteogenesis through TGF-ss Receptor II Binding in Osteoblasts and Activation of Canonical TGF-ss Signaling in MC3T3-E1 Cells and C57BL/6J Mice
T2  - JOURNAL OF NUTRITION
UR  - http://dx.doi.org/10.1093/jn/nxy097
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000441347500011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/64292
VL  - 148
ER  -

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