Table 2.
Direct comparative studies
| Comparison | Target cell | Outcome | References |
|---|---|---|---|
| FGF‐4, PD18 versus TGF‐β2/3 | Mouse MSC |
TGF‐β signaling was sufficient to drive mouse mesodermal stem cells toward the tendon lineage ex vivo and in vitro Examination of the tendon markers Scx (6–8 folds↑), Col1a1 (3–4 folds↑) and the cartilage marker Sox9 (3–4 folds↓) ERK inhibition by PD18 activated Scx and Col1a1 (∼2 folds↑), and had no effect on Sox9 expression FGF does not have a tenogenic effect |
Havis E, et al. Development 2014 |
| Mechanical forces, FGF‐4 versus TGF‐β2 | Mouse TSPC | Based on Scx expression, TGF‐β2 was tenogenic for TSPCs at all stages, while loading was for late‐stage cells only, and FGF‐4 had no effect | Brown JP, et al. J Biomech 2014 |
| Mechanical forces, FGF‐4 versus TGF‐β2 | Mouse MSC and TSPC | TGF‐β2 alone and combined with loading were tenogenic based on increased Scx levels in both MSCs and TSPCs. Loading alone had minimal effect. FGF‐4 downregulated tendon marker levels in MSCs but not in TSPCs | Brown JP, et al. Stem Cell Res Ther 2015 |
| BMP‐2 versus TGF‐β1 versus GDF‐5 | Human MSC |
TGF‐β1 and GDF‐5 show similar COL I (3–5 folds↑), COL II (1–2 folds↑), and SOX9 (1–2 folds↑) expression BMP‐2: COL I (2–3 folds↓), COL II (100 folds↑), SOX9 (1–2 fold↑) |
Murphy MK, et al. Stem Cells 2015 |
| EGF, bFGF, PDGF‐BB, and TGF‐β1 | Human ASC |
TGF‐β1 induced SCX expression 10 folds more than other growth factors on day 7 EGF induced TN‐C (10 folds↑) and COL III (3–5 folds↑) expression on day 14 TGF‐β1 and PDGF‐BB induced COL I expression 10 folds more than other growth factors on day 21 |
Gonçalves AI, et al. PLoS One 2013 |
| TGF‐β1, −2 and −3; GDF‐5, −7 and −8; FGF‐4; IGF‐1; PDGF; EGF and VEGF | Scx‐GFP tenocyte |
TGF‐β1, −2 and −3 were the most potent and induced similar levels of Scx‐GFP expression. GDF‐8 was ∼4 folds less potent than the TGF‐βs Any other cytokines/growth factors examined had no effect |
Maeda T, et al. Curr Biol 2012 |
| IGF‐1 versus TGF‐β3 | Human tenocyte |
Collagen synthesis and expression of Scx and Tnmd TGF‐β3 is more effective than IGF‐1 |
Qiu Y, et al. Cells Tissues Organs 2013 |
| TGF‐β1, BMP‐12, CTGF, and their combinations | Rat BMSC | TGF‐β1 alone significantly and efficiently induced Scx expression and collagen production. TGF‐β1 combined with CTGF elevated Tnmd mRNA and protein expression on day 7 | Yin Z, et al. Stem Cells Translational Medicine 2016 |
| Mechanical forces, FGF, TGF‐β versus PD18 | Chick undifferentiated limb cell |
Both FGF‐4 and TGF‐β2 promote tendon commitment and act downstream of mechanical forces PD18 decreased Scx expression |
Havis E, et al. Development 2016 |
Abbreviations: bFGF, basic fibroblast growth factor; CTGF, connective tissue growth factor; FGF, fibroblast growth factor; IGF‐1, insulin‐like growth factor 1; MSC, mesenchymal stem cells; PDGF‐BB, platelet‐derived growth factors; TGF‐β, transforming growth factor beta; TSPC, tendon stem/progenitor cells.