Table 1.

Summary of osteogenic small molecules, signaling pathways, adjunctive agents and cell lines on which they were evaluated

Molecule name	Mechanisms (Signaling cascades)	Adjuvant treatments	Cell lines
Statins	⊕ Canonical & non-canonical Wnt  ⊕ Estrogen Signaling  ⊕ BMP/Smad  ⊕ RhoA/actin  ⊖ ERK ½  ⊕ P38	Hydroxyapatite PTH BMP-2 Nsi-RNA Estradiol Graphene Oxide	Murine ESC hBMMSC Rat BMMSC MC3T3-E1 MG-63 DPSC
Adenosine	⊕ PI3K pathway  ⊕ Canonical Wnt  ⊕ cAMP signaling	-	Mouse BMMSC hESC hiPSC hBMMSC DPSC
Bisphosphonates	⊖ OPG/Rankl  ⊖ mTOR  ⊕ BMP/Smad	Simvastatin BMP-2	Mouse BMMSC MG-63 Rat AD-MSC MC3T3-E1 Rat BMMSC
Dexamethasone	⊕ Canonical Wnt  ⊕ ERK ½	BMP-2 BMP-2 peptide Hydroxyapatite	SHED Rat BMMSC Rat muscle-derived stromal cell Canine iPSC-derived MSC AD-MSC
Melatonin	⊕ AMPK  ⊕ PKA signaling  ⊕ PKC signaling  ⊕ Neuropeptide Y signaling  ⊕ Canonical Wnt  ⊕ BMP/Smad signaling  ⊕ P38  ⊕ ERK ½  ⊖ OPG/Rankl	Cyclodextrin Retinoic + Butyric + hyaluronic acid BMP-4	Rat BMMSC hBMMSC C2C12 Rabbit DPSC MC3T3-E1 DPSC
Metformin	⊕ AMPK  ⊕ Canonical Wnt  ⊕ BMP/Smad  ⊖ ERK ½  ⊖ P38	-	hCV-MSC MC3T3E1 hiPSC-derived MSC hBMMSC periodontal ligament SC UC-MSC
Phenamil	⊕ BMP/Smad signaling	BMP-2 Nsh-RNA Strontium	AD-MSC MC3T3-E1 DPSC hBMMSC
Parathyroid Hormone	⊕ BMP/Smad signaling  ⊕ cAMP  ⊕ PKC signaling  ⊕ PKA signaling	Vitamin K	Rat BMMSC hBMMSC hAD-MSC Mouse BMMSC
Resveratrol	⊕ ERK ½ OPG/Rankl  ⊕ Sirt1  ⊕ Canonical Wnt	Zoledronic acid	hBMMSC MC3E3-T1 DPSC hESC-derived MSC progenitor Canine AD-MSC Mouse BMMSC Canine BMMSC
Vitamin D3	⊕ Canonical Wnt  ⊕ Sirt1	BMP-2 Vitamin MK-7	hiPSC (105) MC3T3-E1 hBMMSC mouse BMMSC hAD-MSC
T63	⊕ Canonical Wnt  ⊕ BMP/Smad	-	MC3T3-E1
Tetrahydroquinoline	⊕ Canonical Wnt	-	C2C12
Pyrazolopyrimidine	⊕ Canonical Wnt	-	C2C12
Smoothened agonist	⊕ Hedgehog	-	Mouse ESC Mouse iPSC hiPSC
Purmorphamine	⊕ Hedgehog	-	Rat BMMSC DPSC
Rapamycin	⊖ mTOR		BDSC

⊕ :activation of the pathway by small molecule ⊖ : inhibition of the pathway by small molecule