Tcf12, A Member of Basic Helix-Loop-Helix Transcription Factors, Mediates Bone Marrow Mesenchymal Stem Cell Osteogenic Differentiation In Vitro and In Vivo.

Yi, Siqi; Yu, Miao; Yang, Shuang; Miron, Richard John; Zhang, Yufeng (2017). Tcf12, A Member of Basic Helix-Loop-Helix Transcription Factors, Mediates Bone Marrow Mesenchymal Stem Cell Osteogenic Differentiation In Vitro and In Vivo. Stem cells, 35(2), pp. 386-397. AlphaMed Press 10.1002/stem.2491

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Several basic Helix-Loop-Helix transcription factors have recently been identified to regulate mesenchymal stem cell (MSC) differentiation. In the present study, Tcf12 was investigated for its involvement in the osteoblastic cell commitment of MSCs. Tcf12 was found highly expressed in undifferentiated MSCs whereas its expression decreased following osteogenic culture differentiation. Interestingly, Tcf12 endogenous silencing using shRNA lentivirus significantly promoted the differentiation ability of MSCs evaluated by alkaline phosphatase staining, alizarin red staining and expression of osteoblast-specific markers by real-time PCR. Conversely, overexpression of Tcf12 in MSCs suppressed osteoblast differentiation. It was further found that silencing of Tcf12 activated bone morphogenetic protein (BMP) signaling and extracellular signal-regulated kinase (Erk)1/2 signaling pathway activity and upregulated the expression of phospho-SMAD1 and phospho-Erk1/2. A BMP inhibitor (LDN-193189) and Erk1/2 signaling pathway inhibitor (U0126) reduced these findings in the Tcf12 silencing group. Following these in vitro results, a poly-L-lactic acid/Hydroxyappatite scaffold carrying Tcf12 silencing lentivirus was utilized to investigate the repair of bone defects in vivo. The use of Tcf12 silencing lentivirus significantly promoted new bone formation in 3-mm mouse calvarial defects as assessed by micro-CT and histological examination whereas overexpression of Tcf12 inhibited new bone formation. Collectively, these data indicate that Tcf12 is a transcription factor highly expressed in the nuclei of stem cells and its downregulation plays an essential role in osteoblast differentiation partially via BMP and Erk1/2 signaling pathways. Stem Cells 2017;35:386-397.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > School of Dental Medicine > School of Dental Medicine, Restorative Dentistry, Research
04 Faculty of Medicine > School of Dental Medicine > School of Dental Medicine, Periodontics Research
04 Faculty of Medicine > School of Dental Medicine > School of Dental Medicine, Oral Surgery Research
04 Faculty of Medicine > School of Dental Medicine

UniBE Contributor:

Miron, Richard John and Zhang, Yufeng

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1066-5099

Publisher:

AlphaMed Press

Language:

English

Submitter:

Eveline Carmen Schuler

Date Deposited:

10 May 2017 11:09

Last Modified:

10 May 2017 11:09

Publisher DOI:

10.1002/stem.2491

PubMed ID:

27574032

Uncontrolled Keywords:

Bone mesenchymal stem cells, Bone morphogenetic protein signaling, Bone Regeneration, Extracellular signal-regulated kinase 1/2 signaling, Osteogenesis, Tcf12

BORIS DOI:

10.7892/boris.94845

URI:

https://boris.unibe.ch/id/eprint/94845

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