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Domain of dentine sialoprotein mediates proliferation and differentiation of human periodontal ligament stem cells.

ABSTRACT: Classic embryological studies have documented the inductive role of root dentin on adjacent periodontal ligament differentiation. The biochemical composition of root dentin includes collagens and cleavage products of dentin sialophosphoprotein (DSPP), such as dentin sialoprotein (DSP). The high abundance of DSP in root dentin prompted us to ask the question whether DSP or peptides derived thereof would serve as potent biological matrix components to induce periodontal progenitors to further differentiate into periodontal ligament cells. Here, we test the hypothesis that domain of DSP influences cell fate. In situ hybridization and immunohistochemical analyses showed that the COOH-terminal DSP domain is expressed in mouse periodontium at various stages of root development. The recombinant COOH-terminal DSP fragment (rC-DSP) enhanced attachment and migration of human periodontal ligament stem cells (PDLSC), human primary PDL cells without cell toxicity. rC-DSP induced PDLSC cell proliferation as well as differentiation and mineralization of PDLSC and PDL cells by formation of mineralized tissue and ALPase activity. Effect of rC-DSP on cell proliferation and differentiation was to promote gene expression of tooth/bone-relate markers, transcription factors and growth factors. The results for the first time showed that rC-DSP may be one of the components of cell niche for stimulating stem/progenitor cell proliferation and differentiation and a natural scaffold for periodontal regeneration application.

SUBMITTER: Ozer A

PROVIDER: S-EPMC3882282 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Domain of dentine sialoprotein mediates proliferation and differentiation of human periodontal ligament stem cells.

Ozer Alkan A Yuan Guohua G Yang Guobin G Wang Feng F Li Wentong W Yang Yuan Y Guo Feng F Gao Qingping Q Shoff Lisa L Chen Zhi Z Gay Isabel C IC Donly Kevin J KJ MacDougall Mary M Chen Shuo S

PloS one 20131203 12

Classic embryological studies have documented the inductive role of root dentin on adjacent periodontal ligament differentiation. The biochemical composition of root dentin includes collagens and cleavage products of dentin sialophosphoprotein (DSPP), such as dentin sialoprotein (DSP). The high abundance of DSP in root dentin prompted us to ask the question whether DSP or peptides derived thereof would serve as potent biological matrix components to induce periodontal progenitors to further di ...[more]

PMID: 24400037

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Project description:Periodontitis is a common chronic inflammatory oral disease. The objective of periodontal treatment is to control infection whilst regenerating damaged periodontal tissue. The present study aimed to determine the potential effects of pterostilbene (PTE), a representative stilbene compound, on the proliferation and differentiation of human periodontal ligament stem cells (hPDLSCs). Different concentrations (1, 5, 10 and 20 µM) of PTE were applied to hPDLSCs, after which Cell Counting Kit-8 and western blotting assays were performed to examine the protein levels of Ki67, PCNA, p-IκBα, IκBα, Bcl-2, Bax, cleaved caspase3. The effect of PTE on the release of inflammatory factors, including IL-1β, IL-6 and IL-10 was assessed by RT-qPCR. The apoptosis of TNF-α-induced hPDLSCs was evaluated by TUNEL assay and western blotting. Additionally, the role of PTE in hPDLSC mineralization was evaluated using alizarin red staining. The expression levels of mineralization indices, including RUNX2 and ALP were subsequently determined using western blotting. Subsequently, the target of PTE was predicted using TargetNet database and AutoDock v4.2 software and verified using western blotting. The results of the present study revealed that PTE promoted the proliferation of hPDLSCs in a concentration-dependent manner. Furthermore, PTE treatment decreased the release of inflammatory factors and alleviated the apoptosis of TNF-α-induced hPDLSCs. PTE was also demonstrated to promote the formation of mineral nodules in TNF-α-induced hPDLSCs. The Targetnet database, along with molecular docking, indicated that histone deacetylases (HDACs) were the probable targets of PTE upstream of regulating periodontitis. The results of western blotting implied that TNF-α significantly increased expression levels of HDAC2, 4, 6 and 8, whilst PTE treatment markedly decreased HDAC4, 6 and 8 expression in a concentration-dependent manner compared with the TNF-α group, which further confirmed these conclusions. In summary, results of the present study revealed that PTE promoted TNF-α-induced hPDLSC proliferation and differentiation, whilst alleviating inflammation and apoptosis. PTE also inhibited the expression of HDACs, which may be involved in the mechanism of periodontitis.

Dataset Information

Domain of dentine sialoprotein mediates proliferation and differentiation of human periodontal ligament stem cells.

Publications

Domain of dentine sialoprotein mediates proliferation and differentiation of human periodontal ligament stem cells.

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