GDF11 promotes osteogenic/odontogenic differentiation of dental pulp stem cells to accelerate dentin restoration via modulating SIRT3/FOXO3-mediated mitophagy.

Int Immunopharmacol

Department of Stomatology, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, PR China. Electronic address:

Published: December 2024

Background: Growth differentiation factor 11 (GDF11) is considered to be a potential molecular target for treating pulpitis. However, whether GDF11 regulates osteogenic/odontogenic differentiation of dental pulp stem cells (DPSCs) to mediate pulpitis process remains unclear.

Methods: Lipopolysaccharide (LPS) was used to induce inflammation conditions in DPSCs. The levels of GDF11, sirtuin 3 (SIRT3), forkhead box O-3 (FOXO3), osteogenic/odontogenic differentiation-related markers were measured by quantitative real-time PCR (qRT-PCR) and western blot (WB). Immunofluorescence staining was used to measure mitophagy. Mitophagy-related proteins were analyzed by WB, and the levels of inflammation factors were examined using qRT-PCR, ELISA and immunohistochemistry. Alkaline phosphatase activity and alizarin red S intensity were evaluated to assess osteogenic differentiation. Acute pulp (AP) injury rat model was constructed to study the role of oe-GDF11 in vivo.

Results: GDF11 was downregulated in LPS-induced DPSCs, and LPS suppressed osteogenic/odontogenic differentiation and mitophagy. GDF11 overexpression promoted osteogenic/odontogenic differentiation in DPSCs through the activation of mitophagy. Furthermore, GDF11 upregulated SIRT3 to enhance FOXO3 expression by inhibiting its acetylation. GDF11 ameliorated LPS-induced inflammation and promoted osteogenic/odontogenic differentiation in DPSCs via enhancing SIRT3/FOXO3-mediated mitophagy. Besides, GDF11 overexpression suppressed inflammation and promoted dentin repair in AP rat models.

Conclusion: GDF11 promoted SIRT3/FOXO3-mediated mitophagy to accelerate osteogenic/odontogenic differentiation in DPSCs, providing a novel target for pulpitis treatment.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2024.113092DOI Listing

Publication Analysis

Top Keywords

osteogenic/odontogenic differentiation
24
sirt3/foxo3-mediated mitophagy
12
mitophagy gdf11
12
differentiation dpscs
12
gdf11
10
differentiation
8
differentiation dental
8
dental pulp
8
pulp stem
8
stem cells
8

Similar Publications

GDF11 promotes osteogenic/odontogenic differentiation of dental pulp stem cells to accelerate dentin restoration via modulating SIRT3/FOXO3-mediated mitophagy.

Int Immunopharmacol

December 2024

Department of Stomatology, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, PR China. Electronic address:

Background: Growth differentiation factor 11 (GDF11) is considered to be a potential molecular target for treating pulpitis. However, whether GDF11 regulates osteogenic/odontogenic differentiation of dental pulp stem cells (DPSCs) to mediate pulpitis process remains unclear.

Methods: Lipopolysaccharide (LPS) was used to induce inflammation conditions in DPSCs.

View Article and Find Full Text PDF

Background: Research has been conducted to assess the regenerative potential of dental pulp stem cells (DPSCs) following pretreatment of stem cells with certain molecules, bioactive compounds, plant extract and physical stimulation. Andrographis paniculata (AP) herbal extract with important medicinal properties is proven to have a preosteogenic effect on osteoblasts.

Aim: This study aimed to determine the effect of various concentrations of AP extract on the cytotoxicity and osteogenic and odontogenic potential of DPSCs.

View Article and Find Full Text PDF

Scaffold loaded LPS-hUCMSC-sEVs promote Osteo/odontogenic differentiation and angiogenic potential of hDPSCs.

Tissue Cell

December 2024

Department of Pediatric Dentistry, College & Hospital of Stomatology, Guangxi Medical University, No. 10 Shuangyong Road, Nanning 530021, China. Electronic address:

Article Synopsis
  • The study focuses on enhancing vital pulp therapy by using human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hUCMSC-sEVs) with lipopolysaccharide (LPS) pretreatment, which promotes inflammation control and stimulates dental pulp stem cells (hDPSCs) for dentin-pulp complex regeneration.
  • A composite scaffold made of collagen sponge and self-assembling peptide nanofibers (CS/SAPNS) loaded with LPS-hUCMSC-sEVs was developed to facilitate the release of these vesicles to support hDPSC differentiation into osteogenic and angiogenic cells.
  • The results showed that this composite scaffold effectively controlled the
View Article and Find Full Text PDF

Objectives: The aim of this systematic review was to demonstrate the efficacy of topical application of corticosteroids in remineralization of dental pulp tissues to preserve their vitality and function.

Data, Sources And Study Selection: An electronic search was performed using MEDLINE by PubMed, EMBASE, Web of Science (WOS), and Scopus databases. The inclusion criteria were in vitro studies that employed dental pulp tissue obtained from extracted healthy permanent human teeth and were subjected to topical administration of corticosteroids and evaluated tissue remineralization by performing any mineralization assay.

View Article and Find Full Text PDF

Ginsenoside RB1 Influences Macrophage-DPSC Interactions in Inflammatory Conditions.

Int Dent J

August 2024

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xian Jiaotong University, Xi'an, Shaanxi, China; Department of Cariology and Endodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address:

Introduction And Aims: Unresolved inflammation and tissue destruction are supposed to underlie the failure of dental pulp repair. As crucial regulators of the injury response, dental pulp stem cells (DPSCs) play a key role in pulp tissue repair and regeneration. M2 macrophages have been demonstrated to induce osteogenic/odontogenic differentiation of DPSCs.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!