Insulin‐like growth factor 1 can promote proliferation and osteogenic differentiation of human dental pulp stem cells via m<scp>TOR</scp> pathway

Feng, Xingmei; Huang, Dan; Lü, Xiaohui; Feng, Guoliang; Xing, Jing; Lü, Jun; Xu, Ke; Xia, Weiwei; Meng, Yan; Tao, Tao; Li, Liren; Gu, Zhifeng

doi:10.1111/dgd.12179

Cited by 82 publications

(61 citation statements)

References 57 publications

(89 reference statements)

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“…COL-I comprises almost 90% of organic material during the formation of inorganic bone matrix to support the structure of osteogenesis333536. OCN is a small c-carboxyglutamate protein, which is synthesized only by mature cementoblasts, osteoblasts and odontoblasts, and its function is controlled by RUNX2 in the later-stage of mineralized tissues353637. Our previous studies have proved that IGF-1 can stimulate the odonto/osteogenic differentiation of SCAPs and PDLSCs in vitro 68.…”

Section: Discussionmentioning

confidence: 99%

IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla

Ma¹,

Liu

Lin

et al. 2016

Sci Rep

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Insulin-like growth factor-1 (IGF-1) and its receptor IGF-1R play a paramount role in tooth/bone formation while hsa-let-7c actively participates in the osteogenic differentiation of mesenchymal stem cells. However, the interaction between IGF-1/IGF-1R and hsa-let-7c on the committed differentiation of stem cells from apical papilla (SCAPs) remains unclear. In this study, human SCAPs were isolated and treated with IGF-1 and hsa-let-7c over/low-expression viruses. The odonto/osteogenic differentiation of these stem cells and the involvement of mitogen-activated protein kinase (MAPK) pathway were subsequently investigated. Alizarin red staining showed that hsa-let-7c low-expression can significantly promote the mineralization of IGF-1 treated SCAPs, while hsa-let-7c over-expression can decrease the calcium deposition of IGF-1 treated SCAPs. Western blot assay and real-time reverse transcription polymerase chain reaction further demonstrated that the expression of odonto/osteogenic markers (ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, COL-I/COL-I, DSPP/DSP, and DMP-1/DMP-1) in IGF-1 treated SCAPs were significantly upregulated in Let-7c-low group. On the contrary, hsa-let-7c over-expression could downregulate the expression of these odonto/osteogenic markers. Moreover, western blot assay showed that the JNK and p38 MAPK signaling pathways were activated in Let-7c-low SCAPs but inhibited in Let-7c-over SCAPs. Together, the IGF-1/IGF-1R/hsa-let-7c axis can control the odonto/osteogenic differentiation of IGF-1-treated SCAPs via the regulation of JNK and p38 MAPK signaling pathways.

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Section: Discussionmentioning

confidence: 99%

IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla

Ma¹,

Liu

Lin

et al. 2016

Sci Rep

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“…Although IGF1 has been reported previously to promote the differentiation of human dental pulp stem cells via mTor (Feng et al, 2014) and MAPK/Stat-3 (Vandomme et al, 2014) signalling pathways there is only a limited literature describing IGFBP-2 and/or IGFBP-3 expression and activity during osteogenic differentiation. A direct effect of IGFBP-2 on the osteoblastic differentiation of rat calvarial cells via a receptor tyrosine phosphatase β (RPTPβ) based mechanism was recently reported (Xi et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

IGFBP-2 and -3 co-ordinately regulate IGF1 induced matrix mineralisation of differentiating human dental pulp cells

et al. 2016

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Human dental pulp cells (DPCs), which are known to contain a subset of stem cells capable of reforming a dentin and pulp-like complex upon in vivo transplantation, were isolated from third molars of three healthy donors and differentiated to a matrix mineralisation phenotype using by culture in dexamethasone and l-ascorbic acid. qRT-PCR analysis of insulin-like growth factor ( IGF) axis gene expression indicated that all genes, except insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein-1 ( IGFBP-1), were expressed in DPCs. During differentiation upregulation of insulin-like growth factor binding protein-2 (IGFBP-2) and downregulation of insulin-like growth factor binding protein-3 (IGFBP-3) expression was observed. Changes in IGFBP-2 and IGFBP-3 mRNA expression were confirmed at the protein level by ELISA of DPC conditioned medium functional analysis indicated that IGF1 stimulated the differentiation of DPCs and that the activity of the growth factor was enhanced by pre-complexation with IGFBP-2 but inhibited by pre-complexation with IGFBP-3. Therefore changes in IGFBP-2 and -3 expression during differentiation form part of a co-ordinated functional response to enhance the pro-differentiative action of IGF1 and represent a novel mechanism for the regulation of DPC differentiation.

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“…On the other hand, TORC 2 is involved in the cytoskeleton reorganization and cell survival [ 78 ]. In the concept of DSC differentiation, the mTOR signaling pathway is activated in the process of osteogenic differentiation of hDPSCs [ 80 ].…”

Section: Mtor Signaling Pathwaymentioning

confidence: 99%

Signaling Pathways in Dental Stem Cells During Their Maintenance and Differentiation

Liu

Zhou

et al. 2016

Dental Stem Cells

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Insulin‐like growth factor 1 can promote proliferation and osteogenic differentiation of human dental pulp stem cells via mTOR pathway

Cited by 82 publications

References 57 publications

IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla

IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla

IGFBP-2 and -3 co-ordinately regulate IGF1 induced matrix mineralisation of differentiating human dental pulp cells

Signaling Pathways in Dental Stem Cells During Their Maintenance and Differentiation

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