Supplementary Figure 1 a b c d e 1 2 cGMP levels (pmol/ml) vehicle

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Supplementary Figure 1 a b c d e 1 2 cGMP levels (pmol/ml) vehicle 1 2 cGMP levels (pmol/ml) vehicle Wnt3a c 10 0 10 1 10 2 10 3 0.61% 2.28% 96.33% 0.78% B1 B2 B3 B4 FL3-PI 0.53% 95.88% 1.13% 0.73% 2.02% 96.44% 0.81% 0.96% 2.43% 95.4% 1.21% FL1-Annexin V FITC Ctrl Tadalafil 5 μM Tadalafil 10 μM Tadalafil 1 μM 4 ** L Lef1 Luc. activity (RLU) Wnt3a 3 † ‡ 2 1 ** 1 5 10 Vardenafil (μM) d 10 0 10 1 10 2 10 3 0.44% 2.71% 96.37% 1.02% B1 B2 B3 B4 FL3-PI 0.53% 2.28% 95.88% 1.13% 0.64% 2.16% 96.47% 0.73% 0.78% 2.81% 95.16% 1.25% FL1-Annexin V FITC Ctrl KT5823 1 μM KT5823 5 μM KT5823 0.2 μM e 10 0 10 1 10 2 10 3 0.20% 1.06% 96.74% 2.00% B1 B2 B3 B4 FL3-PI 0.27% 0.87% 95.44% 3.41% 0.31% 1.07% 93.58% 5.04% 0.14% 0.72% 96.28% 2.86% FL1-Annexin V FITC Ctrl Tadalafil 5 μM Tadalafil 10 μM Tadalafil 1 μM Supplementary Figure 1

Supplementary Figure 2 a b 0.4 0.8 1.2 1.6 b-catenin mRNA levels 0.4 0.8 1.2 1.6 b-catenin mRNA levels Tadalafil (μM) 5 10 b β-catenin p45- Wnt3a Tada. - + β-actin 1.0 0.6 1.1 0.6 1.0 1.0 0.9 0.8 L Supplementary Figure 2

Supplementary Figure 3 b a SFRP1+/- SFRP1-/- 100 200 300 400 500 600 700 TRAP staining positive cells/mm3 SFRP1+/- SFRP1-/- Mice Tad. (mg/kg) 75 a 50 mm 20 mm SFRP1+/- SFRP1-/- Normal saline Tadalafil (75mg/kg) Supplementary Figure 3

Supplementary Figure 4 a b c d 0.5 1.0 1.5 2.0 2.5 3.0 3.5 0.1 0.2 0.3 0.5 1.0 1.5 2.0 2.5 3.0 3.5 0.1 0.2 0.3 0.4 0.6 1/mm 0.7 mm Tadalafil (mg/kg) 75 45 SFRP1-/- TbTh TbSp SFRP1+/- Tadalafil (mg/kg) TbN * ** ‡ a b c d Supplementary Figure 4