Table 1. Relation between the different cell treatments and the BMP signaling pathway indicated by IPA® software at days 7, 14, 21, and 28. ASCs were treated according to the groups: OM (osteogenic medium); BMP-2 (OM and BMP-2); RA (OM and retinoic acid, RA); BMP-2+RA (OM, BMP-2, and RA). MC3T3-E1 was used as positive control. r<0.05 represents statistically significant difference. Positive z-score indicates up-regulation (highlighted in orange) and negative z-score implies down-regulation (highlighted in blue) of the signaling pathway evidenced by the IPA® software (v=versus).

BMP signaling pathway – Day 7			BMP signaling pathway – Day 21
Observation	Z-score	ρ value	Observation	Z-score	ρ value
OM v MC3T3-E1	0		OM v MC3T3-E1	0
BMP-2 v MC3T3-E1	0		BMP-2 v MC3T3-E1	0
RA v MC3T3-E1	0		RA v MC3T3-E1	0
BMP-2+RA v MC3T3-E1	0		BMP-2+RA v MC3T3-E1	0
BMP-2 v OM	0		BMP-2 v OM	1.342	5.14E-11
RA v OM	0		RA v OM	0.447	5.14E-11
BMP-2+RA v OM	0		BMP-2+RA v OM	-1.342	5.14E-11
BMP-2 v RA	1	4.51E-09	BMP-2 v RA	0.447	5.14E-11
BMP-2 v BMP-2+RA	-1	4.51E-09	BMP-2 v BMP-2+RA	1.342	5.14E-11
RA v BMP-2+RA	-1	4.51E-09	RA v BMP-2+RA	0.447	5.14E-11
BMP signaling pathway – Day 14			BMP signaling pathway – Day 28
Observation	Z-score	ρ value	Observation	Z-score	ρ value
OM v MC3T3-E1	-2	4.41E-9	OM v MC3T3-E1	0
BMP-2 v MC3T3-E1	0		BMP-2 v MC3T3-E1	0
RA v MC3T3-E1	-1	4.41E-9	RA v MC3T3-E1	0
BMP-2+RA v MC3T3-E1	-1	8.8E-9	BMP-2+RA v MC3T3-E1	0
BMP-2 v OM	1	5.14E-11	BMP-2 v OM	0
RA v OM	2.236	5.14E-11	RA v OM	1	8.8E-9
BMP-2+RA v OM	1.342	4.41E-9	BMP-2+RA v OM	2	8.8E-9
BMP-2 v RA	1	8.8E-9	BMP-2 v RA	-1	8.8E-9
BMP-2 v BMP-2+RA	-1	8.8E-9	BMP-2 v BMP-2+RA	-2	8.8E-9
RA v BMP-2+RA	-0.447	5.14E-11	RA v BMP-2+RA	0
DIFFERENTIATION OF BONE-FORMING CELLS at day 14
Observation	ρ value	Activation z-score	Molecules
OM v MC3T3-E1	2.20E-06	-2	Ca2+,SMAD1,SMAD4,SMAD5
RA v OM	1.24E-07	2	Ca2+,SMAD1,SMAD4,SMAD5
BMP-2+RA v OM	1.24E-07	2	Ca2+,SMAD1,SMAD4,SMAD5