Biphasic Effect of ATP on In Vitro Mineralization of Dental Pulp Cells

Techatharatip, Oranuch; Nowwarote, Nunthawan; Taebunpakul, Suthisa; Pavasant, Prasit

doi:10.1002/jcb.26206

Cited by 11 publications

(11 citation statements)

References 34 publications

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“…Mechanistically, mechanical force stimulated ATP release via connexin43 and the intracellular calcium signaling pathway 26 . It has been reported that ATP supplementation in osteogenic medium enhanced osteogenic marker gene expression and mineralization in several cell types 27,[35][36][37] . In the present study, short-term ATP treatment prior to osteogenic induction did not influence osteogenic marker gene expression or mineralization by hPDLs.…”

Section: Discussionmentioning

confidence: 99%

Intermittent compressive force promotes osteogenic differentiation in human periodontal ligament cells by regulating the transforming growth factor-β pathway

et al. 2019

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Mechanical force regulates periodontal ligament cell (PDL) behavior. However, different force types lead to distinct PDL responses. Here, we report that pretreatment with an intermittent compressive force (ICF), but not a continuous compressive force (CCF), promoted human PDL (hPDL) osteogenic differentiation as determined by osteogenic marker gene expression and mineral deposition in vitro. ICF-induced osterix (OSX) expression was inhibited by cycloheximide and monensin. Although CCF and ICF significantly increased extracellular adenosine triphosphate (ATP) levels, pretreatment with exogenous ATP did not affect hPDL osteogenic differentiation. Gene-expression profiling of hPDLs subjected to CCF or ICF revealed that extracellular matrix (ECM)-receptor interaction, focal adhesion, and transforming growth factor beta (TGF-β) signaling pathway genes were commonly upregulated, while calcium signaling pathway genes were downregulated in both CCF-and ICF-treated hPDLs. The TGFB1 mRNA level was significantly increased, while those of TGFB2 and TGFB3 were decreased by ICF treatment. In contrast, CCF did not modify TGFB1 expression. Inhibiting TGF-β receptor type I or adding a TGF-β1 neutralizing antibody attenuated the ICF-induced OSX expression. Exogenous TGF-β1 pretreatment promoted hPDL osteogenic marker gene expression and mineral deposition. Additionally, pretreatment with ICF in the presence of TGF-β receptor type I inhibitor attenuated the ICF-induced mineralization. In conclusion, this study reveals the effects of ICF on osteogenic differentiation in hPDLs and implicates TGF-β signaling as one of its regulatory mechanisms.

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Section: Discussionmentioning

confidence: 99%

Intermittent compressive force promotes osteogenic differentiation in human periodontal ligament cells by regulating the transforming growth factor-β pathway

et al. 2019

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“…A mineralization assay was performed as described previously (Techatharatip, Nowwarote, Taebunpakul, & Pavasant, 2018). Cells were fixed with cold methanol for 10 min.…”

Section: In Vitro Mineralizationmentioning

confidence: 99%

Cyclic tensile force stimulates BMP9 synthesis and in vitro mineralization by human periodontal ligament cells

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Niyompanich

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et al. 2018

Journal Cellular Physiology

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Periodontal ligament (PDL) cells are mechanosensitive and have the potential to differentiate into osteoblast-like cells under the influence of cyclic tensile force (CTF). CTF modulates the expression of regulatory proteins including bone morphogenetic proteins (BMPs), which are essential for the homeostasis of the periodontium. Among the BMPs, BMP9 is one of the most potent osteogenic BMPs. It is yet unknown whether CTF affects the expression of BMP9 and mineralization. Here, we demonstrated that continuously applied CTF for only the first 6 hr stimulated the synthesis of BMP9 and induced mineral deposition within 14 days by human PDL cells. Stimulation of BMP9 expression depended on ATP and P2Y receptors. Apyrase, an ecto-ATPase, inhibited CTF-mediated ATP-induced BMP9 expression. The addition of ATP increased the expression of BMP9. Loss of function experiments using suramin (a broad-spectrum P2Y antagonist), MRS2179 (a specific P2Y receptor antagonist), MRS 2365 (a specific P2Y agonist), U-73122 (a phospholipase C [PLC] inhibitor), and thapsigargin (enhancer of intracytosolic calcium) revealed the participation of P2Y in regulating the expression of BMP9. This was mediated by an increased level of intracellular Ca through the PLC pathway. A neutralizing anti-BMP9 antibody decreased mineral deposition, which was stimulated by CTF for almost 45% indicating a role of BMP9 in an in vitro mineralization. Collectively, our findings suggest an essential modulatory role of CTF in the homeostasis and regeneration of the periodontium.

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“…ATP, which has been considered as an energy source, is also involved in the determination of cell fate, proliferation, metabolism, differentiation and apoptosis . Thereby, it is possible that ATP plays a vital role in promoting or preventing malignant transformation.…”

Section: Introductionmentioning

confidence: 99%

Extracellular ATP promotes breast cancer invasion and epithelial‐mesenchymal transition via hypoxia‐inducible factor 2α signaling

et al. 2019

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Extracellular ATP has been shown to play an important role in invasion and the epithelial‐mesenchymal transition (EMT) process in breast cancer; however, the mechanism is unclear. Here, by using a cDNA microarray, we demonstrated that extracellular ATP could stimulate hypoxia‐inducible factor (HIF) signaling and upregulate hypoxia‐inducible factor 1/2α (HIF‐1/2α) expression. After knocking down HIF‐1/2α using siRNA, we found that ATP‐driven invasion and EMT were significantly attenuated via HIF2A‐siRNA in breast cancer cells. By using ChIP assays, we revealed that the biological function of extracellular ATP in invasion and EMT process depended on HIF‐2α direct targets, among which lysyl oxidase‐like 2 (LOXL2) and matrix metalloproteinase‐9 (MMP‐9) mediated ATP‐driven invasion, and E‐cadherin and Snail mediated ATP‐driven EMT, respectively. In addition, using silver staining and mass spectrometry, we found that phosphoglycerate kinase 1 (PGK1) could interact with HIF‐2α and mediate ATP‐driven HIF‐2α upregulation. Furthermore, we demonstrated that expressions of HIF‐2α and its target proteins could be regulated via ATP by AKT‐PGK1 pathway. Using a Balb/c mice model, we illustrated the function of HIF‐2α in promoting tumor growth and metastasis in vivo. Moreover, by exploring online databases, we found that molecules involved in ATP‐HIF‐2α signaling were highly expressed in human breast carcinoma tissues and were associated with poor prognosis. Altogether, these findings suggest that extracellular ATP could promote breast carcinoma invasion and EMT via HIF‐2α signaling, which may be a potential target for future anti–metastasis therapy.

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Biphasic Effect of ATP on In Vitro Mineralization of Dental Pulp Cells

Cited by 11 publications

References 34 publications

Intermittent compressive force promotes osteogenic differentiation in human periodontal ligament cells by regulating the transforming growth factor-β pathway

Intermittent compressive force promotes osteogenic differentiation in human periodontal ligament cells by regulating the transforming growth factor-β pathway

Cyclic tensile force stimulates BMP9 synthesis and in vitro mineralization by human periodontal ligament cells

Extracellular ATP promotes breast cancer invasion and epithelial‐mesenchymal transition via hypoxia‐inducible factor 2α signaling

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