Open AccessEndogenous GDF11 regulates odontogenic differentiation of dental pulp stem cells
Author(s) -
Qi Xingying,
Xiao Qingyue,
Sheng Rui,
Jiang Shuang,
Yuan Quan,
Liu Weiqing
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15754
Subject(s) - dental pulp stem cells , wnt signaling pathway , gene knockdown , stem cell , endogeny , microbiology and biotechnology , biology , cellular differentiation , growth differentiation factor , ameloblast , transcription factor , runx2 , bone morphogenetic protein , signal transduction , gene , dentistry , genetics , endocrinology , medicine , enamel paint
Dental stem cell‐based tooth regeneration is the futuristic treatment for missing teeth. Growth differentiation factor 11 (GDF11), a novel member of the TGF‐beta superfamily, has been reported to play a critical role in regulating stem cell differentiation. However, the role of endogenous GDF11 during dental stem cell differentiation remains unknown. Here, we have shown that GDF11 was highly expressed in dental pulp tissues in both mouse and human. Knockdown of endogenous GDF11 in human dental pulp stem cells (hDPSCs) led to comparable proliferation and migration but attenuated odontogenic differentiation as evidenced by alkaline phosphatase and Alizarin Red S staining. In addition, transcriptional levels of odontogenic‐related genes were significantly down‐regulated according to real‐time polymerase chain reaction. Mechanistically, we performed RNA sequencing analysis and found that silencing of endogenous GDF11 compromised the process of ossification and osteoblast differentiation, especially down‐regulated transcription expression of Wnt pathway‐specific genes. Immunofluorescence staining also showed diminished β‐catenin expression and nuclei accumulation after knockdown of endogenous GDF11 in hDPSCs. In summary, our results suggested that endogenous GDF11 positively regulate odontogenic differentiation of hDPSCs through canonical Wnt/β‐catenin signalling pathway.