Objective: To explore the effects of transforming growth factor -beta 2 (TGF-beta 2) and TGF-beta 1 on the odontogenic and osteogenic differentiation of mesenchymal stem cells (MSCs). Design: We used lentiviral transduction to knock down TGF-beta 1 or TGF-beta 2 in stem cells from dental apical papilla (SCAPs), and to generate bone marrow mesenchymal stem cells (BMSCs) with overexpression of TGF-beta 1 or TGF-beta 2. We investigated the odontogenic and osteogenic differentiation abilities of these transductants in vitro and in vivo. Results: In vitro, TGF-beta 2 knockdown in SCAPs reduced the expression of odontoblast-related markers DSPP and DMP-1, and increased the expression of osteoblast-related markers OCN and RUNX-2. Conversely, TGF-beta 1 knockdown had the opposite effects. TGF-beta 2 overexpression promoted expression of odontoblast-related markers in BMSCs at early differentiation, but inhibited the expression of odontoblast-related markers at later stages. TGF-beta 2 overexpression attenuated expression of osteogenic-related markers in BMSCs, while TGF-beta 1 over expression enhanced odontoblast-related and osteoblast-related markers. SCAP or BMSC transductants were transplanted underneath kidneys in vivo. Masson staining showed that knockdown of TGF-beta 1, but not TGF-beta 2 promoted the expression of type I collagen in SCAPs. Immunohistochemical staining showed that TGF-beta 2 knockdown inhibited DSPP expression in SCAPs, but TGF-beta 1 knockdown had no obvious effect on DSPP expression. In vivo, TGF-beta 1 overexpression and TGF-beta 2 overexpression had no effect on the expression of type I collagen and DSPP in BMSCs. Conclusions: TGF-beta 2 promotes odontogenic differentiation of SCAPs and attenuates osteogenic differentiation of SCAPs and BMSCs. TGF-beta 1 promotes osteogenic differentiation of BMSCs and plays a complex role in regulating odontogenic differentiation of MSCs.