TAFA2 Induces Skeletal (Stromal) Stem Cell Migration Through Activation of Rac1-p38 Signaling
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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.
In: Stem Cells, Vol. 37, No. 3, 2019, p. 407-416.Research output: Contribution to journal › Journal article › Research › peer-review
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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
PY - 2019
Y1 - 2019
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 2018.
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 2018.
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
AN - SCOPUS:85058850237
VL - 37
SP - 407
EP - 416
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 3
ER -
ID: 212124696