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

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

  • Int Immunopharmacol. 2024 Dec 5;142(Pt B):113092. doi: 10.1016/j.intimp.2024.113092.
Mingsi Deng 1 Ruimin Tang 2 Yani Xu 3 Yafen Xu 3 Liangjian Chen 4
Affiliations

Affiliations

  • 1 Department of Stomatology, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, PR China; Department of Orthodontics, Changsha Stomatological Hospital, Changsha City, Hunan Province, PR China.
  • 2 Department of Stomatology, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, PR China.
  • 3 Department of Orthodontics, Changsha Stomatological Hospital, Changsha City, Hunan Province, PR China.
  • 4 Department of Stomatology, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, PR China. Electronic address: chenliangjian0248@163.com.
Abstract

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.

Keywords

FOXO3; GDF11; Mitophagy; Osteogenic/odontogenic differentiation; Pulpitis; SIRT3.

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