Table 5 ALK5 TGFβ inhibitors downregulate the expression of fibrotic markers following fibrotic nodule formation assay in human primary MPCs.

From: Preclinical validation of TGFβ inhibitors as a novel therapeutic strategy for post-traumatic heterotopic ossification

Treatment Conditions

Relative Gene Expression Levels [Gene/GAPDH]

FN1

SERPINE1

MMP9

CDH2

Control

0.95 ± 0.09

1.00 ± 0.13

1.18 ± 0.57

1.03 ± 0.11

TGFβ1 10 ng/mL

3.86 ± 1.49

6.69 ± 4.35

1.66 ± 1.51

3.02 ± 2.03

SB431542 1 µM ± TGFβ1

0.96 ± 0.26, p = 0.02

0.66 ± 0.25, p = 0.04

0.76 ± 0.16, p = 0.31

1.04 ± 0.13, p = 0.14

SB431542 3 µM + TGFβ1

0.80 ± 0.14, p = 0.02

0.51 ± 0.32, p = 0.04

0.84 ± 0.57, p = 0.35

1.11 ± 0.21, p = 0.17

LY2157299 1 µM + TGFβ1

1.02 ± 0.18, p = 0.02

1.29 ± 0.45, p = 0.04

0.77 ± 0.48, p = 0.23

0.95 ± 0.20, p = 0.16

LY2157299 3 µM + TGFβ1

0.83 ± 0.14, p = 0.02

0.85 ± 0.43, p = 0.04

0.79 ± 0.64, p = 0.23

0.95 ± 0.14, p = 0.14

Halofuginone 10 nM + TGFβ1

3.84 ± 1.38, p = 0.48

8.05 ± 5.25, p = 0.04

2.68 ± 2.44, p = 0.29

3.47 ± 3.20, p = 0.19

Halofuginone 30 nM + TGFβ1

3.81 ± 2.16, p = 0.48

7.73 ± 3.83, p = 0.20

1.98 ± 0.89, p = 0.45

3.09 ± 2.14, p = 0.25

SIS3 10 µM + TGFβ1

3.68 ± 1.39, p = 0.26

6.50 ± 4.58, p = 0.35

1.65 ± 2.17, p = 0.50

1.82 ± 1.00, p = 0.23

SIS3 20 µM + TGFβ1

4.03 ± 1.31, p = 0.14

7.17 ± 4.61, p = 0.20

2.61 ± 2.51, p = 0.48

2.96 ± 2.41, p = 0.25

  1. Primary MPCs were treated with ALK5 inhibitors (SB431542 or Galunisertib/LY2157299) and SMAD3 inhibitors (Halofuginone or SIS3) and TGFβ [10 ng/mL] for 4 days following fibrotic nodule formation assay conditions. Relative expression levels were analyzed by qRT-PCR for the fibrotic markers FN1, SERPINE1, MMP9, and CDH2. GAPDH was used as a housekeeping control gene. Non-treated control was used as a reference to calculate relative gene expression levels. DMSO treatment was used as vehicle control. Average ± SE from three to seven independent donors. Adjusted p-value was calculated by 1-tail student’s T-test in comparison with TGFβ treatment alone.
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