TGF-β2 and TGF-β1 differentially regulate the odontogenic and osteogenic differentiation of mesenchymal stem cells

Jingzhi Li; Lihong Ge; Yuming Zhao; Yue Zhai; Nanquan Rao; Xiaojing Yuan; Jie Yang; Jing Li; Shi Yu

doi:10.1016/j.archoralbio.2022.105357

TGF-β2 and TGF-β1 differentially regulate the odontogenic and osteogenic differentiation of mesenchymal stem cells

Arch Oral Biol. 2022 Mar:135:105357. doi: 10.1016/j.archoralbio.2022.105357. Epub 2022 Jan 15.

Authors

Jingzhi Li¹, Lihong Ge², Yuming Zhao², Yue Zhai³, Nanquan Rao⁴, Xiaojing Yuan², Jie Yang², Jing Li⁵, Shi Yu⁶

Affiliations

¹ Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China; Department of Pediatric Dentistry, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
³ Department of Stomatology, Beijing Children's Hospital, Capital Medical University, Beijing, China.
⁴ Hospital of Stomatology Kunming Medical University, Department of Dental Research, Kunming, China.
⁵ Dental Medical Center, China-Japan Friendship Hospital, Beijing, China.
⁶ Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China. Electronic address: yushi20071120@126.com.

PMID: 35085927
DOI: 10.1016/j.archoralbio.2022.105357

Abstract

Objective: To explore the effects of transforming growth factor-β2 (TGF-β2) and TGF-β1 on the odontogenic and osteogenic differentiation of mesenchymal stem cells (MSCs).

Design: We used lentiviral transduction to knock down TGF-β1 or TGF-β2 in stem cells from dental apical papilla (SCAPs), and to generate bone marrow mesenchymal stem cells (BMSCs) with overexpression of TGF-β1 or TGF-β2. We investigated the odontogenic and osteogenic differentiation abilities of these transductants in vitro and in vivo.

Results: In vitro, TGF-β2 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-β1 knockdown had the opposite effects. TGF-β2 overexpression promoted expression of odontoblast-related markers in BMSCs at early differentiation, but inhibited the expression of odontoblast-related markers at later stages. TGF-β2 overexpression attenuated expression of osteogenic-related markers in BMSCs, while TGF-β1 overexpression enhanced odontoblast-related and osteoblast-related markers. SCAP or BMSC transductants were transplanted underneath kidneys in vivo. Masson staining showed that knockdown of TGF-β1, but not TGF-β2 promoted the expression of type I collagen in SCAPs. Immunohistochemical staining showed that TGF-β2 knockdown inhibited DSPP expression in SCAPs, but TGF-β1 knockdown had no obvious effect on DSPP expression. In vivo, TGF-β1 overexpression and TGF-β2 overexpression had no effect on the expression of type I collagen and DSPP in BMSCs.

Conclusions: TGF-β2 promotes odontogenic differentiation of SCAPs and attenuates osteogenic differentiation of SCAPs and BMSCs. TGF-β1 promotes osteogenic differentiation of BMSCs and plays a complex role in regulating odontogenic differentiation of MSCs.

Keywords: Bone marrow stem cell; Odontogenic differentiation; Osteogenic differentiation; Stem cell from apical papilla; TGF-β1; TGF-β2.

MeSH terms

Cell Differentiation
Cell Proliferation
Cells, Cultured
Dental Papilla
Mesenchymal Stem Cells*
Osteogenesis*
Transforming Growth Factor beta1
Transforming Growth Factor beta2

Substances

Transforming Growth Factor beta1
Transforming Growth Factor beta2