Fibroblast growth factor 2 induces mesenchymal stem cells to differentiate into tenocytes through the MAPK pathway

Abstract

Mesenchymal stem cells (MSCs) differentiate into numerous different cell types and thus have therapeutic potential for tissue engineering, anti‑inflammatory and immunomodulatory purposes. FGF2 may affect the biological behavior of MSCs. MSCs were transduced with either adenovirus‑null vector/green fluorescent protein (GFP) or a vector encoding for the overexpression of FGF2/GFP. The expression of FGF2 was demonstrated to be significantly higher in MSC (FGF2) compared with MSC (vector) by qPCR and western blot analysis. In order to investigate the function of FGF2 in MSCs over time, it was observed that FGF2 stimulates cell proliferation and induces cell differentiation by activating the mitogen‑activated protein kinase (MAPK) signaling pathway. Following blockade of the FGF2‑induced activation of the extracellular signal‑regulated kinase pathway by overexpression of sprouty isoforms, the marker of differentiation markedly decreased. Altogether, the results demonstrated a novel cell biological mechanism that FGF2 differentiates into tenocytes and the MAPK pathway is key in differentiation.

Early cellular responses of BMSCs genetically modified with bFGF/BMP2 co-cultured with ligament fibroblasts in a three-dimensional model in vitro

“…In our study, for the AdbFGF group, our results demonstrated that cell proliferation and the expression of SCX and COL1 in the BMSCs was markedly enhanced, indicating a shift of BMSCs towards the more mature state of fibroblast-like cells following the gene transfer of bFGF. Our findings collaborate with the findings of the in vitro model by Cai et al, which suggested that bFGF may be an important regulator of the proliferation and differentiation of BMSCs (33). As regards the ligament fibroblasts, cell proliferation was markedly enhanced, and this was accompanied by the decreased expression of COL1 and COL3.…”

Effects of ERK/p38 MAPKs signaling pathways on MTA-mediated osteo/odontogenic differentiation of stem cells from apical papilla: a vitro study

“…MAPKs include 3 families: extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and p38 MAPK [24]. Many factors are involving in the differentiation of Mesenchymal stem cells via MAPK signaling pathways [25,26]. Previous study has shown that MTA could activate MAPK signaling pathways to promote osteo/odontogenic differentiation of dental pulp cells in vitro [27].…”

Mechanisms of Action of Multipotent Mesenchymal Stromal Cells in Tendon Disease

“…A promising stepwise differentiation approach has also been reported using TGF-β1 followed by connective tissue growth factor (CTGF) [54]. Growth factors are commonly delivered as culture medium supplements, but, e.g., FGF-2-transduced MSCs have been used as well [89]. Further tenogenic differentiation approaches based on genetic modifications include the forced expression of the tenogenic transcription factors scleraxis [10,152] 79,81,87], both being used based on evidence that physical cues such as scaffold anisotropy and stiffness direct MSC fate.…”

“…To understand if physiological stimuli could promote the same distinct tenogenic phenotype as artificial TGF-β concentrations, it would be helpful to gain further insight into the downstream signaling networks and their possible interfaces. So far, however, tenogenic signaling has mainly been investigated following growth factor stimulation [67, 82,89,90]. Only few studies have attempted to elucidate the signaling pathways activated in MSC in response to mechanical load or scaffold topographical cues, focusing on the role of rho/ ROCK [154,155].…”