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IGFBP5 promotes angiogenic and neurogenic differentiation potential of dental pulp stem cells
Author(s) -
Li Jing,
Diao Shu,
Yang Haoqing,
Cao Yangyang,
Du Juan,
Yang Dongmei
Publication year - 2019
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/dgd.12632
Subject(s) - dental pulp stem cells , nestin , angiogenesis , neurosphere , neurogenesis , stem cell , biology , microbiology and biotechnology , cancer research , immunology , pathology , medicine , neural stem cell , endothelial stem cell , adult stem cell , in vitro , genetics
Dental stem cells for dental pulp regeneration have become a new strategy for pulpitis treatment. Angiogenesis and neurogenesis play a vital role in the pulp‐dentin complex regeneration, and appropriate growth factors will promote the process of angiogenesis and neurogenesis. Insulin‐like growth factor‐binding protein 5 (IGFBP5) is involved in the regulation of tooth growth and development. A previous study showed that IGFBP5 enhanced osteo/odontogenic differentiation of dental stem cells. Our research intends to reveal the function of IGFBP5 in the angiogenic and neurogenic differentiation of human dental stem cells. Human dental pulp stem cells (DPSCs) were used in the present study. Lentiviral IGFBP5 shRNA was used to silence the IGFBP5. Retroviruses expressing Wild‐type IGFBP5 were used to over‐express IGFBP5. Angiogenic and neurogenic differentiation were carried out by in vitro study. Real‐time RT‐PCR and western blot results showed that over‐expression of IGFBP5 upregulated the expressions of angiogenic markers, including VEGF, PDGFA and ANG‐1, and neurogenic markers, including NCAM, TH, Nestin, βIII‐tubulin, and TH, in DPSCs. Moreover, microscope observation confirmed that over‐expression of IGFBP5 enhanced neurosphere formation in DPSCs in size and amount. Immunofluorescence staining results showed that over‐expression of IGFBP5 also prompted the percentage of Nestin and βIII‐tubulin positive neurospheres in DPSCs. While depletion of IGFBP5 downregulated the expressions of VEGF, PDGFA, ANG‐1, NCAM, TH, Nestin, βIII‐tubulin, and TH, it decreased the neurosphere formation and percentage of Nestin and βIII‐tubulin positive neurospheres in DPSCs. In conclusion, our results revealed that IGFBP5 promoted angiogenic and neurogenic differentiation potential of DPSCs in vitro and provided the possible potential target for enhancing directed differentiation of dental stem cells and dental pulp‐dentin functional regeneration.