TAFA2 Induces Skeletal (Stromal) Stem Cell Migration Through Activation of Rac1-p38 Signaling

Abbas Jafari, Adiba Isa, Li Chen, Nicholas Ditzel, Walid Zaher, Linda Harkness, Hans E Johnsen, Basem M Abdallah, Christian Clausen, Moustapha Kassem

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

58 Downloads (Pure)

Resumé

Understanding the mechanisms regulating recruitment of human skeletal (stromal or mesenchymal) stem cells (hMSC) to sites of tissue injury is a prerequisite for their successful use in cell replacement therapy. Chemokine-like protein TAFA2 is a recently discovered neurokine involved in neuronal cell migration and neurite outgrowth. Here, we demonstrate a possible role for TAFA2 in regulating recruitment of hMSC to bone fracture sites. TAFA2 increased the in vitro trans-well migration and motility of hMSC in a dose-dependent fashion and induced significant morphological changes including formation of lamellipodia as revealed by high-content-image analysis at single-cell level. Mechanistic studies revealed that TAFA2 enhanced hMSC migration through activation of the Rac1-p38 pathway. In addition, TAFA2 enhanced hMSC proliferation, whereas differentiation of hMSC toward osteoblast and adipocyte lineages was not altered. in vivo studies demonstrated transient upregulation of TAFA2 gene expression during the inflammatory phase of fracture healing in a closed femoral fracture model in mice, and a similar pattern was observed in serum levels of TAFA2 in patients after hip fracture. Finally, interleukin-1β was found as an upstream regulator of TAFA2 expression. Our findings demonstrate that TAFA2 enhances hMSC migration and recruitment and thus is relevant for regenerative medicine applications. Stem Cells 2019;37:407–416.

OriginalsprogEngelsk
TidsskriftStem Cells
Vol/bind37
Udgave nummer3
Sider (fra-til)407-416
ISSN1066-5099
DOI
StatusUdgivet - 1. mar. 2019

Fingeraftryk

Stromal Cells
Mesenchymal Stromal Cells
Cell Movement
Closed Fractures
Pseudopodia
Fracture Healing
Regenerative Medicine
Femoral Fractures
Bone Fractures
Osteoblasts
Adipocytes
Up-Regulation
Cell Proliferation
Wounds and Injuries
Serum
Proteins

Bibliografisk note

© 2018 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2018.

Citer dette

Jafari, Abbas ; Isa, Adiba ; Chen, Li ; Ditzel, Nicholas ; Zaher, Walid ; Harkness, Linda ; Johnsen, Hans E ; Abdallah, Basem M ; Clausen, Christian ; Kassem, Moustapha. / TAFA2 Induces Skeletal (Stromal) Stem Cell Migration Through Activation of Rac1-p38 Signaling. I: Stem Cells. 2019 ; Bind 37, Nr. 3. s. 407-416.
@article{d40b79652d30449ca113147ea6ab2ca5,
title = "TAFA2 Induces Skeletal (Stromal) Stem Cell Migration Through Activation of Rac1-p38 Signaling",
abstract = "Understanding the mechanisms regulating recruitment of human skeletal (stromal or mesenchymal) stem cells (hMSC) to sites of tissue injury is a prerequisite for their successful use in cell replacement therapy. Chemokine-like protein TAFA2 is a recently discovered neurokine involved in neuronal cell migration and neurite outgrowth. Here, we demonstrate a possible role for TAFA2 in regulating recruitment of hMSC to bone fracture sites. TAFA2 increased the in vitro trans-well migration and motility of hMSC in a dose-dependent fashion and induced significant morphological changes including formation of lamellipodia as revealed by high-content-image analysis at single-cell level. Mechanistic studies revealed that TAFA2 enhanced hMSC migration through activation of the Rac1-p38 pathway. In addition, TAFA2 enhanced hMSC proliferation, whereas differentiation of hMSC toward osteoblast and adipocyte lineages was not altered. in vivo studies demonstrated transient upregulation of TAFA2 gene expression during the inflammatory phase of fracture healing in a closed femoral fracture model in mice, and a similar pattern was observed in serum levels of TAFA2 in patients after hip fracture. Finally, interleukin-1β was found as an upstream regulator of TAFA2 expression. Our findings demonstrate that TAFA2 enhances hMSC migration and recruitment and thus is relevant for regenerative medicine applications. Stem Cells 2019;37:407–416.",
keywords = "Fracture healing, Mesenchymal stem (stromal) cell, Migration, Regenerative medicine, TAFA2",
author = "Abbas Jafari and Adiba Isa and Li Chen and Nicholas Ditzel and Walid Zaher and Linda Harkness and Johnsen, {Hans E} and Abdallah, {Basem M} and Christian Clausen and Moustapha Kassem",
note = "{\circledC} 2018 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2018.",
year = "2019",
month = "3",
day = "1",
doi = "10.1002/stem.2955",
language = "English",
volume = "37",
pages = "407--416",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press, Inc.",
number = "3",

}

TAFA2 Induces Skeletal (Stromal) Stem Cell Migration Through Activation of Rac1-p38 Signaling. / Jafari, Abbas; Isa, Adiba; Chen, Li; Ditzel, Nicholas; Zaher, Walid; Harkness, Linda; Johnsen, Hans E; Abdallah, Basem M; Clausen, Christian; Kassem, Moustapha.

I: Stem Cells, Bind 37, Nr. 3, 01.03.2019, s. 407-416.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - TAFA2 Induces Skeletal (Stromal) Stem Cell Migration Through Activation of Rac1-p38 Signaling

AU - Jafari, Abbas

AU - Isa, Adiba

AU - Chen, Li

AU - Ditzel, Nicholas

AU - Zaher, Walid

AU - Harkness, Linda

AU - Johnsen, Hans E

AU - Abdallah, Basem M

AU - Clausen, Christian

AU - Kassem, Moustapha

N1 - © 2018 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2018.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Understanding the mechanisms regulating recruitment of human skeletal (stromal or mesenchymal) stem cells (hMSC) to sites of tissue injury is a prerequisite for their successful use in cell replacement therapy. Chemokine-like protein TAFA2 is a recently discovered neurokine involved in neuronal cell migration and neurite outgrowth. Here, we demonstrate a possible role for TAFA2 in regulating recruitment of hMSC to bone fracture sites. TAFA2 increased the in vitro trans-well migration and motility of hMSC in a dose-dependent fashion and induced significant morphological changes including formation of lamellipodia as revealed by high-content-image analysis at single-cell level. Mechanistic studies revealed that TAFA2 enhanced hMSC migration through activation of the Rac1-p38 pathway. In addition, TAFA2 enhanced hMSC proliferation, whereas differentiation of hMSC toward osteoblast and adipocyte lineages was not altered. in vivo studies demonstrated transient upregulation of TAFA2 gene expression during the inflammatory phase of fracture healing in a closed femoral fracture model in mice, and a similar pattern was observed in serum levels of TAFA2 in patients after hip fracture. Finally, interleukin-1β was found as an upstream regulator of TAFA2 expression. Our findings demonstrate that TAFA2 enhances hMSC migration and recruitment and thus is relevant for regenerative medicine applications. Stem Cells 2019;37:407–416.

AB - Understanding the mechanisms regulating recruitment of human skeletal (stromal or mesenchymal) stem cells (hMSC) to sites of tissue injury is a prerequisite for their successful use in cell replacement therapy. Chemokine-like protein TAFA2 is a recently discovered neurokine involved in neuronal cell migration and neurite outgrowth. Here, we demonstrate a possible role for TAFA2 in regulating recruitment of hMSC to bone fracture sites. TAFA2 increased the in vitro trans-well migration and motility of hMSC in a dose-dependent fashion and induced significant morphological changes including formation of lamellipodia as revealed by high-content-image analysis at single-cell level. Mechanistic studies revealed that TAFA2 enhanced hMSC migration through activation of the Rac1-p38 pathway. In addition, TAFA2 enhanced hMSC proliferation, whereas differentiation of hMSC toward osteoblast and adipocyte lineages was not altered. in vivo studies demonstrated transient upregulation of TAFA2 gene expression during the inflammatory phase of fracture healing in a closed femoral fracture model in mice, and a similar pattern was observed in serum levels of TAFA2 in patients after hip fracture. Finally, interleukin-1β was found as an upstream regulator of TAFA2 expression. Our findings demonstrate that TAFA2 enhances hMSC migration and recruitment and thus is relevant for regenerative medicine applications. Stem Cells 2019;37:407–416.

KW - Fracture healing

KW - Mesenchymal stem (stromal) cell

KW - Migration

KW - Regenerative medicine

KW - TAFA2

U2 - 10.1002/stem.2955

DO - 10.1002/stem.2955

M3 - Journal article

C2 - 30485583

VL - 37

SP - 407

EP - 416

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 3

ER -