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Activation of TGF-β Canonical and Noncanonical Signaling in Bovine Lactoferrin-Induced Osteogenic Activity of C3H10T1/2 Mesenchymal Stem Cells.

Abstract

Lactoferrin (LF) is known to modulate the bone anabolic effect. Previously, we and others reported that the effects of LF on the bone may be conferred by the stimulation of transforming growth factor β (TGF-β) signaling in the preosteoblast. However, the underlying molecular mechanisms of LF-induced osteogenic differentiation of mesenchymal stem cells (MSCs) has not been identified. In this study, we tested the hypothesis that the effects of LF on osteogenesis of MSCs required mediation by TGF-β Receptors and activating TGF-β signaling pathway. Using siRNA silencing technology, the knockdown of TGF-β Receptor II (TβRII) could significantly attenuate LF's effect on the proliferation rate and alkaline phosphatase (ALP) activity of MSCs. It indicated that LF induced osteogenic activity that is dependent on TβRII in C3H10T1/2. Subsequently, it was shown that LF activated Smad2. Downregulating TGF-β Receptor I (TβRI) with SB431542 attenuated the expression of p-Smad2 and p-P38, also the LF-induced the osteogenic activity. Besides, the stimulation by LF on the expression of Osteocalcin (OCN), Osteopontin (OPN), Collagen-2a1 (Col2a1), and Fibroblast Growth Factor 2 (FGF2) were abolished by SB431542. These results confirmed that LF induced osteogenic activity though the TGF-β canonical and noncanonical signaling pathway. This study provided the first evidence of the signaling mechanisms of LF's effect on osteogenesis in MSCs.

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  • Authors+Show Affiliations

    ,

    Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. liyixuan9735@126.com.

    ,

    Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. zw_7431@163.com. Beijing Laboratory of Food Quality and Safety, China Agricultural University, Beijing 100083, China. zw_7431@163.com.

    ,

    Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. renfazheng@cau.edu.cn. Key Laboratory of Functional Dairy, co-constructed by Ministry of Education and Beijing Government, China Agricultural University, Beijing 100083, China. renfazheng@cau.edu.cn.

    Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. guohuiyuan@cau.edu.cn. Key Laboratory of Functional Dairy, co-constructed by Ministry of Education and Beijing Government, China Agricultural University, Beijing 100083, China. guohuiyuan@cau.edu.cn.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31200471

    Citation

    Li, Yixuan, et al. "Activation of TGF-β Canonical and Noncanonical Signaling in Bovine Lactoferrin-Induced Osteogenic Activity of C3H10T1/2 Mesenchymal Stem Cells." International Journal of Molecular Sciences, vol. 20, no. 12, 2019.
    Li Y, Zhang W, Ren F, et al. Activation of TGF-β Canonical and Noncanonical Signaling in Bovine Lactoferrin-Induced Osteogenic Activity of C3H10T1/2 Mesenchymal Stem Cells. Int J Mol Sci. 2019;20(12).
    Li, Y., Zhang, W., Ren, F., & Guo, H. (2019). Activation of TGF-β Canonical and Noncanonical Signaling in Bovine Lactoferrin-Induced Osteogenic Activity of C3H10T1/2 Mesenchymal Stem Cells. International Journal of Molecular Sciences, 20(12), doi:10.3390/ijms20122880.
    Li Y, et al. Activation of TGF-β Canonical and Noncanonical Signaling in Bovine Lactoferrin-Induced Osteogenic Activity of C3H10T1/2 Mesenchymal Stem Cells. Int J Mol Sci. 2019 Jun 13;20(12) PubMed PMID: 31200471.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Activation of TGF-β Canonical and Noncanonical Signaling in Bovine Lactoferrin-Induced Osteogenic Activity of C3H10T1/2 Mesenchymal Stem Cells. AU - Li,Yixuan, AU - Zhang,Wei, AU - Ren,Fazheng, AU - Guo,Huiyuan, Y1 - 2019/06/13/ PY - 2019/04/30/received PY - 2019/05/26/revised PY - 2019/05/31/accepted PY - 2019/6/16/entrez KW - Lactoferrin KW - TGF-β/Smad2 signaling pathway KW - mesenchymal stem cells KW - osteogenic JF - International journal of molecular sciences JO - Int J Mol Sci VL - 20 IS - 12 N2 - Lactoferrin (LF) is known to modulate the bone anabolic effect. Previously, we and others reported that the effects of LF on the bone may be conferred by the stimulation of transforming growth factor β (TGF-β) signaling in the preosteoblast. However, the underlying molecular mechanisms of LF-induced osteogenic differentiation of mesenchymal stem cells (MSCs) has not been identified. In this study, we tested the hypothesis that the effects of LF on osteogenesis of MSCs required mediation by TGF-β Receptors and activating TGF-β signaling pathway. Using siRNA silencing technology, the knockdown of TGF-β Receptor II (TβRII) could significantly attenuate LF's effect on the proliferation rate and alkaline phosphatase (ALP) activity of MSCs. It indicated that LF induced osteogenic activity that is dependent on TβRII in C3H10T1/2. Subsequently, it was shown that LF activated Smad2. Downregulating TGF-β Receptor I (TβRI) with SB431542 attenuated the expression of p-Smad2 and p-P38, also the LF-induced the osteogenic activity. Besides, the stimulation by LF on the expression of Osteocalcin (OCN), Osteopontin (OPN), Collagen-2a1 (Col2a1), and Fibroblast Growth Factor 2 (FGF2) were abolished by SB431542. These results confirmed that LF induced osteogenic activity though the TGF-β canonical and noncanonical signaling pathway. This study provided the first evidence of the signaling mechanisms of LF's effect on osteogenesis in MSCs. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/31200471/Activation_of_TGF-β_Canonical_and_Noncanonical_Signaling_in_Bovine_Lactoferrin-Induced_Osteogenic_Activity_of_C3H10T1/2_Mesenchymal_Stem_Cells L2 - http://www.mdpi.com/resolver?pii=ijms20122880 DB - PRIME DP - Unbound Medicine ER -