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

2019 ◽  
Vol 20 (12) ◽  
pp. 2880 ◽  
Author(s):  
Yixuan Li ◽  
Wei Zhang ◽  
Fazheng Ren ◽  
Huiyuan Guo
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Bovine Lactoferrin ◽  
Osteogenic Activity ◽  
Β Receptor ◽  
Noncanonical Signaling

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.

scholarly journals Expression of transforming growth factor β receptor II in mesenchymal stem cells from systemic sclerosis patients

BMJ Open ◽  
2013 ◽  
Vol 3 (1) ◽  
pp. e001890 ◽  
Author(s):  
Valérie Vanneaux ◽  
Dominique Farge-Bancel ◽  
Séverine Lecourt ◽  
Julie Baraut ◽  
Audrey Cras ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Systemic Sclerosis ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Β Receptor

scholarly journals Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate regenerative wound healing via transforming growth factor-β receptor inhibition

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Zhang ◽  
Yingjin Pan ◽  
Yanhong Liu ◽  
Xiheng Li ◽  
Liang Tang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Scar Formation ◽  
Myofibroblast Differentiation ◽  
Receptor Inhibition ◽  
Β Receptor

Abstract Background Scar formation is a common consequence of skin wound healing, and no effective treatment exists. Umbilical cord blood mesenchymal stem cells (UCB-MSCs) can improve wound healing; however, the role of UCB-MSCs remains unclear and whether they can ameliorate scar formation has not been fully elucidated. Methods To determine the function of UCB-MSCs, we examined and compared the therapeutic effects of UCB-MSCs and UCB-MSC-derived exosomes (UCB-MSC-exo) on skin healing in rats. Moreover, UCB-MSC-exo-specific miRNAs were identified and their effects in inhibiting the human dermal fibroblast (HDF) differentiation into myofibroblasts were investigated. Results Both UCB-MSCs and UCB-MSC-exo accelerated wound closure; reduced scar formation; improved the regeneration of skin appendages, nerves, and vessels; and regulated the natural distribution of collagen fibers in wound healing. Additionally, UCB-MSC-exo suppressed the excessive formation of myofibroblasts and collagen I and increased the proliferation and migration of skin cells in vivo and in vitro. Functional analysis showed that UCB-MSC-derived miRNAs were closely related to the transforming growth factor-β (TGF-β) signaling pathway, which could induce myofibroblast differentiation. We identified abundant miRNAs that were highly expressed in UCB-MSC-exo. miR-21-5p and miR-125b-5p were predicted to contribute to TGF-β receptor type II (TGFBR2) and TGF-β receptor type I (TGFBR1) inhibition, respectively. Using miRNA mimics, we found that miR-21-5p and miR-125b-5p were critical for anti-myofibroblast differentiation in the TGF-β1-induced HDF. Conclusion The effect of UCB-MSCs in stimulating regenerative wound healing might be achieved through exosomes, which can be, in part, through miR-21-5p- and miR-125b-5p-mediated TGF-β receptor inhibition, suggesting that UCB-MSC-exo might represent a novel strategy to prevent scar formation during wound healing.

scholarly journals Synthesis of embryonic tendon-like tissue by human marrow stromal/mesenchymal stem cells requires a three-dimensional environment and transforming growth factor β3

2010 ◽  
Vol 29 (8) ◽  
pp. 668-677 ◽  
Author(s):  
Zoher Kapacee ◽  
Ching-Yan Chloé Yeung ◽  
Yinhui Lu ◽  
David Crabtree ◽  
David F. Holmes ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Three Dimensional ◽  
Embryonic Tendon

scholarly journals Mesenchymal Stem Cells and Transforming Growth Factor-β3 (TGF-β3) to Enhance the Regenerative Ability of an Albumin Scaffold in Full Thickness Wound Healing

2018 ◽  
Vol 9 (4) ◽  
pp. 65 ◽  
Author(s):  
Dale Feldman ◽  
John McCauley
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Surgical Treatment ◽  
Growth Factor ◽  
Healing Rate ◽  
Pressure Ulcers ◽  
Transforming Growth Factor ◽  
Bed Rest ◽  
Full Thickness ◽  
Non Surgical Treatment

Pressure ulcers are one of the most common forms of skin injury, particularly in the spinal cord injured (SCI). Pressure ulcers are difficult to heal in this population requiring at least six months of bed rest. Surgical treatment (grafting) is the fastest recovery time, but it still requires six weeks of bed rest plus significant additional costs and a high recurrence rate. A significant clinical benefit would be obtained by speeding the healing rate of a non-surgical treatment to close to that of surgical treatment (approximately doubling of healing rate). Current non-surgical treatment is mostly inactive wound coverings. The goal of this project was to look at the feasibility of doubling the healing rate of a full-thickness defect using combinations of three treatments, for the first time, each shown to increase healing rate: application of transforming growth factor-β3 (TGF-β3), an albumin based scaffold, and mesenchymal stem cells (MSCs). At one week following surgery, the combined treatment showed the greatest increase in healing rate, particularly for the epithelialization rate. Although the target level of a 100% increase in healing rate over the control was not quite achieved, it is anticipated that the goal would be met with further optimization of the treatment.

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