Phosphorylation of Runx2, induced by cyclic mechanical tension via ERK1/2 pathway, contributes to osteodifferentiation of human periodontal ligament fibroblasts

Ren, Dunqiang; Wei, Fulan; Hu, Lihua; Yang, Shuangyan; Wang, Chunling; Yuan, Xiao

doi:10.1002/jcp.24972

Cited by 40 publications

(46 citation statements)

References 54 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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“…12% deformation was selected according to the results from a finite element model, which predicts the deformation of PDLCs (human maxillary central incisor, mid‐root level) subjected to horizontal displacements under physiological loading conditions . Although currently there is no consensus about the loading conditions such as stress type, magnitude, frequency, and duration that best represent the force loading on periodontal ligament during OTM, the strain application system and the parameters adopted in our study have been frequently used and validated to promote osteogenic differentiation of PDLCs in previous studies …”

Section: Discussionmentioning

confidence: 99%

“…In the tension side of the OTM, new bone forms as a result of tensile strain on the PDLCs. Accordingly, the expressions of osteogenic markers in PDLCs, such as core‐binding factor α1 (Cbfα1, also known as RUNX2), osterix (OSX), osteocalcin (OCN), collagen type I (COL I), and alkaline phosphatase (ALP), are found to be elevated under tensile strain, suggesting an osteoblastic phenotype of PDLCs …”

Section: Introductionmentioning

confidence: 99%

TAZ contributes to osteogenic differentiation of periodontal ligament cells under tensile stress

Wang

et al. 2019

J of Periodontal Research

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Background and objective Bone remodeling during orthodontic treatment is achieved by the osteogenesis of human periodontal ligament cells (PDLCs) subjected to mechanical loadings. Transcriptional co‐activator with PDZ‐binding motif (TAZ) mediates bone remodeling in response to extracellular mechanical signals. This study aims to investigate the role of TAZ in osteogenesis of PDLCs under tensile strain. Materials and methods A uniaxial cyclic tensile stress (CTS) at 12% elongation and 6 cycles/min (5 s on and 5 s off) was applied to PDLCs. The osteogenic differentiation was determined by the protein and gene expressions of osteogenic markers using qRT‐PCR and Western blot, respectively, and further by alkaline phosphatase (ALP) activity and Alizarin Red S staining. The interaction of TAZ with core‐binding factor α1 (Cbfα1) was examined by co‐immunoprecipitation. The immunofluorescence histochemistry was used to examine the nucleus aggregation of TAZ and the reorganization of actin filaments. Moreover, small interfering RNA‐targeting TAZ (TAZsiRNA) was used for TAZ inhibition and Y‐27632 was employed for Ras homologue‐associated coiled‐coil protein kinase (ROCK) signaling blockage. Results CTS clearly stimulated the nucleus accumulation of TAZ and its interaction with Cbfα1. CTS‐induced osteogenesis in PDLCs was significantly abrogated by the infection with TAZsiRNA, as shown by the decreased stained nodules and protein expressions of Cbfα1, collagen type I, osterix, and osteocalcin, along with the inhibition of β‐catenin signaling. Moreover, ROCK inhibition by Y‐27632 hindered TAZ nucleus aggregation and its binding with Cbfα1, which subsequently lead to the decreased osteoblastic differentiation of PDLCs. Conclusions Taken together, we propose that TAZ nucleus localization and its interaction with Cbfα1 are essential for the CTS‐induced osteogenic differentiation in PDLCs. And such TAZ activation by CTS could be mediated by ROCK signaling, indicating the pivot role of ROCK‐TAZ pathway for PDLCs differentiation.

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“…[11] In periodontal ligament stem cells, Ren et al demonstrated that cyclic mechanical tension mimicking occlusal force resulted in increased osteogenic differentiation via ERK1/2-mediated runt-related transcription factor 2 (Runx2) activation. [12] …”

Section: Introductionmentioning

confidence: 99%

Nonmineralized and Mineralized Collagen Scaffolds Induce Differential Osteogenic Signaling Pathways in Human Mesenchymal Stem Cells

Zhou

Ren

Bischoff

et al. 2017

Adv Healthcare Materials

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The instructive capabilities of extracellular matrix components in progenitor cell differentiation have recently generated significant interest in the development of bioinspired materials for regenerative applications. Previously, a correlation was described between the osteogenic capabilities of nanoparticulate mineralized collagen glycosaminoglycan scaffolds (MC-GAG) and an autogenous activation of small mothers against decapentaplegic ( Smad1/5) in the canonical bone morphogenetic protein receptor (BMPR) pathway with a diminished extracellular signal regulated kinase 1/2 (ERK1/2) activation when compared to nonmineralized collagen glycosaminoglycan scaffolds (Col-GAG). This work utilizes a canonical BMPR inhibitor (dorsomorphin homologue 1, DMH1) and an inhibitor of the mitogen activated protein kinase/ERK kinase (MEK)/(ERK) cascade (PD98059) to characterize the necessity of each pathway for osteogenesis. While DMH1 inhibits runt-related transcription factor 2 (Runx2) and bone sialoprotein II (BSPII) gene expression of primary human mesenchymal stem cells (hMSCs) on MC-GAG, PD98059 inhibits BSPII expression on Col-GAG independent of Runx2 expression. DMH1 inhibits mineralization on both Col-GAG and MC-GAG, however, PD98059 only inhibits mineralization on Col-GAG. DMH1 inhibits both Smad1/5 phosphorylation and Runx2 protein expression, whereas PD98059 inhibits ERK1/2 and c-Jun amino-terminal kinase 1/2 (JNK1/2) phosphorylation without affecting Runx2. Thus, activation of the canonical BMPR signaling is necessary for osteogenic differentiation and mineralization of hMSCs on Col-GAG or MC-GAG. The MEK/ERK cascade, intimately tied to JNK activation, is necessary for Runx2-independent osteogenesis on Col-GAG, while completely dispensable in osteogenesis on MC-GAG.

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Phosphorylation of Runx2, induced by cyclic mechanical tension via ERK1/2 pathway, contributes to osteodifferentiation of human periodontal ligament fibroblasts

Cited by 40 publications

References 54 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

TAZ contributes to osteogenic differentiation of periodontal ligament cells under tensile stress

Nonmineralized and Mineralized Collagen Scaffolds Induce Differential Osteogenic Signaling Pathways in Human Mesenchymal Stem Cells

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