Fluid Shear Stress Stimulates Osteogenic Differentiation of Human Periodontal Ligament Cells via the Extracellular Signal‐Regulated Kinase 1/2 and p38 Mitogen‐Activated Protein Kinase Signaling Pathways

Tang, Min; Peng, Zhuli; Mai, Zhihui; Chen, Lin; Mao, Qinghui; Chen, Zheng; Chen, Qi; Liu, Limin; Wang, Yuxuan; Hong, Ai

doi:10.1902/jop.2014.140244

Cited by 38 publications

(39 citation statements)

References 26 publications

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“…In this study, upregulation of osteogenic gene expression was observed in cells under continuous tensile strain (Li et al, 2014; Ren et al, 2015; Shen et al, 2014; Tang et al, 2014; Wei et al, 2008; Zhang et al, 2015). Animal experiments have demonstrated that continuous tensile strain generated by orthodontic appliances also upregulates osteogenic markers in PDL during orthodontic tooth movement (Kawarizadeh et al, 2005; Kim et al, 2012; Watanabe et al, 2008).…”

Section: Discussionmentioning

confidence: 54%

“…Numerous studies have shown that mechanical strain induces osteogenic differentiation of PDL cells by increasing osteogenic genes such as RUNX2 and OPN (Li et al, 2014; Ren et al, 2015; Tang et al, 2014; Zhang et al, 2015). Therefore, we investigated the effects of continuous tensile strain from the device on the osteogenic gene expression in HPL cells.…”

Section: Resultsmentioning

confidence: 99%

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Novel device for application of continuous mechanical tensile strain to mammalian cells

et al. 2017

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During orthodontic tooth movement, the periodontal ligament (PDL) is exposed to continuous mechanical strain. However, many researchers have applied cyclic tensile strain, not continuous tensile strain, to PDL cells in vitro because there has been no adequate device to apply continuous tensile strain to cultured cells. In this study, we contrived a novel device designed to apply continuous tensile strain to cells in culture. The continuous tensile strain was applied to human immortalized periodontal ligament cell line (HPL cells) and the cytoskeletal structures of HPL cells were examined by immunohistochemistry. The expression of both inflammatory and osteogenic markers was also examined by real-time reverse transcription polymerase chain reaction. The osteogenic protein, Osteopontin (OPN), was also detected by western blot analysis. The actin filaments of HPL cells showed uniform arrangement under continuous tensile strain. The continuous tensile strain increased the expression of inflammatory genes such as IL-1β, IL-6, COX-2 and TNF-α, and osteogenic genes such as RUNX2 and OPN in HPL cells. It also elevated the expression of OPN protein in HPL cells. These results suggest that our new simple device is useful for exploring the responses to continuous tensile strain applied to the cells.

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Section: Discussionmentioning

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Novel device for application of continuous mechanical tensile strain to mammalian cells

et al. 2017

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“…Mechanical stimulation, such as shear, tensile, centrifugation, and vibration, has been shown to regulate osteogenic differentiation [28][29][30][31][32] . Cyclic tensile strain significantly enhanced RUNX2 and OSX expression in human periodontal ligament stem cells (hPDLSCs) 33 .…”

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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“…This observation correlated with the increase in Bmp2 , Bmp4 and Axin2 gene expression. BM-MSCs, periodontal ligament cells and dental pulp cells exposed to calcium-derived biomaterials have been reported to induce the upregulation of Bmp2 mRNA expression [8,39,40]. These studies implicated MAPK activity and AP-1 transcription factors in such effects [8,41].…”

Section: Discussionmentioning

confidence: 99%

Extracellular calcium promotes bone formation from bone marrow mesenchymal stem cells by amplifying the effects of BMP-2 on SMAD signalling

et al. 2017

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Understanding the molecular events that regulate osteoblast differentiation is essential for the development of effective approaches to bone regeneration. In this study, we analysed the osteoinductive properties of extracellular calcium in bone marrow-derived mesenchymal stem cell (BM-MSC) differentiation. We cultured BM-MSCs in 3D gelatin scaffolds with Ca2+ and BMP-2 as osteoinductive agents. Early and late osteogenic gene expression and bone regeneration in a calvarial critical-size defect model demonstrate that extracellular Ca2+ enhances the effects of BMP-2 on Osteocalcin, Runx2 and Osterix expression and promotes bone regeneration in vivo. Moreover, we analysed the molecular mechanisms involved and observed an antagonistic effect between Ca2+ and BMP-2 on SMAD1/5, ERK and S6K signalling after 24 hours. More importantly, a cooperative effect between Ca2+ and BMP-2 on the phosphorylation of SMAD1/5, S6, GSK3 and total levels of β-CATENIN was observed at a later differentiation time (10 days). Furthermore, Ca2+ alone favoured the phosphorylation of SMAD1, which correlates with the induction of Bmp2 and Bmp4 gene expression. These data suggest that Ca2+ and BMP-2 cooperate and promote an autocrine/paracrine osteogenic feed-forward loop. On the whole, these results demonstrate the usefulness of calcium-based bone grafts or the addition of exogenous Ca2+ in bone tissue engineering.

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Fluid Shear Stress Stimulates Osteogenic Differentiation of Human Periodontal Ligament Cells via the Extracellular Signal‐Regulated Kinase 1/2 and p38 Mitogen‐Activated Protein Kinase Signaling Pathways

Abstract: FSS is an effective approach for stimulating osteogenic differentiation of hPDLCs. The ERK1/2 and p38 MAPK signaling pathways are involved in this cellular process.

Cited by 38 publications

References 26 publications

Novel device for application of continuous mechanical tensile strain to mammalian cells

Novel device for application of continuous mechanical tensile strain to mammalian cells

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

Extracellular calcium promotes bone formation from bone marrow mesenchymal stem cells by amplifying the effects of BMP-2 on SMAD signalling

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