Progranulin promotes osteogenic differentiation of human periodontal ligament stem cells via tumor necrosis factor receptors to inhibit TNF‐α sensitized NF‐kB and activate ERK/JNK signaling

Chen, Jing; Yu, Miao; Li, Xiao; Qi-zhong, Sun; Yang, Chengzhe; Yang, Pishan

doi:10.1111/jre.12720

Cited by 19 publications

(19 citation statements)

References 37 publications

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“…This indicates that both JNK and ERK1/2 can be involved in active FGF23 increase in starved MLO-Y4 cells and suggests that the effect of 17β-E2, in maintaining FGF23 levels at the control values, is due to its ability to inhibit these kinases and/or factors downstream from their signaling pathway. Nuclear factor kappa B (NF-κB) is one of the transcription factors activated by ERK1/2 and involved in bone loss following estrogen withdrawal and in FGF23 regulation [46][47][48][49]. The activation of NF-κB is due to the phosphorylation of the IKK kinase, which phosphorylates and inhibits IKB-α, the endogenous inhibitor of NF-κB, by promoting its degradation.…”

Section: Role Of Map Kinases On Osia-induced Intra-and Extracellular ...mentioning

confidence: 99%

Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol

Domazetovic

Falsetti

Ciuffi

et al. 2022

IJMS

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The discovery that osteocytes secrete phosphaturic fibroblast growth factor 23 (FGF23) has defined bone as an endocrine organ. However, the autocrine and paracrine functions of FGF23 are still unknown. The present study focuses on the cellular and molecular mechanisms involved in the complex control of FGF23 production and local bone remodeling functions. FGF23 was assayed using ELISA kit in the presence or absence of 17β–estradiol in starved MLO-Y4 osteocytes. In these cells, a relationship between oxidative stress-induced apoptosis and up-regulation of active FGF23 levels due to MAP Kinases activation with involvement of the transcriptional factor (NF-kB) has been demonstrated. The active FGF23 increase can be due to up-regulation of its expression and post-transcriptional modifications. 17β–estradiol prevents the increase of FGF23 by inhibiting JNK and NF-kB activation, osteocyte apoptosis and by the down-regulation of osteoclastogenic factors, such as sclerostin. No alteration in the levels of dentin matrix protein 1, a FGF23 negative regulator, has been determined. The results of this study identify biological targets on which drugs and estrogen may act to control active FGF23 levels in oxidative stress-related bone and non-bone inflammatory diseases.

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Section: Role Of Map Kinases On Osia-induced Intra-and Extracellular ...mentioning

confidence: 99%

Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol

Domazetovic

Falsetti

Ciuffi

et al. 2022

IJMS

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“…Lacey et al 27 showed that TNF‑α inhibits the expression of ALP and Runx2 and the activity of ALP during the osteoblastic differentiation of BMSCs. Previous studies also demonstrated that TNF significantly inhibited the osteogenic differentiation of hPDLSCs through the NF-κB, MAPK, and mTOR signaling pathways 28 , 29 . In the present study, TNF-α at 1, 10, and 20 ng/mL reduced the OSX and Runx2 protein levels in a concentration-dependent manner.…”

Section: Discussionmentioning

confidence: 84%

miR-23b mediates TNF-α-Inhibited Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Targeting Runx2

Sun¹,

Li²,

Ban³

et al. 2021

Int. J. Med. Sci.

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Periodontitis is the most prevalent oral infection disease, which causes the destruction of periodontal supporting tissues and eventual tooth loss. This study aimed to investigate the molecular mechanism of miRNA-23b (miR-23b) in regulating the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in an inflammatory environment. Results revealed that tumor necrosis factor-α (TNF-α), a notoriously inflammatory cytokine, remarkably attenuated the osteogenic differentiation of hPDLSCs, which were partially rescued by SKL2001 (Wnt/β-catenin agonist). We further explored the underlying roles of miRNAs involved in TNF-α-inhibited osteogenesis of hPDLSCs. The miR-23b significantly increased with TNF-α stimulation, which was abolished by SKL2001. Similar to the effect of TNF-α, miR-23b agonist (agomir-23b) dramatically reduced the expression of runt-related transcription factor 2 (Runx2) and suppressed the osteogenic differentiation of hPDLSCs. The inhibition of miR-23b significantly increased Runx2, which is the major transcription factor during osteogenesis, thereby indicating that miR-23b was an endogenous regulator of Runx2 in hPDLSCs. Bioinformatic analysis and dual luciferase reporter assays confirmed that Runx2 was a target gene of miR-23b. Furthermore, the gain function assay of Runx2 revealed that the Runx2 overexpression efficiently reversed the suppression of the osteogenic differentiation of hPDLSCs with miR-23b agonist, suggesting that the suppressing effect of miR-23b on osteogenesis was mediated by Runx2 inhibition. Our study clarified that miR-23b mediated the TNF-α-inhibited osteogenic differentiation of hPDLSCs by targeting Runx2. Therefore, the expanded function of miR-23b in the osteogenesis of hPDLSCs under inflammatory conditions. This study might provide new insights and a novel therapeutic target for periodontitis.

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“…MAPK signaling pathways were reported to participate in regulating osteogenic differentiation of PDLSCs 17,18 . Therefore, we explored the possible role of MAPK signaling pathways in PPi regulation of PDLSC osteogenic differentiation.…”

Section: Resultsmentioning

confidence: 99%

Pyrophosphate inhibits periodontal ligament stem cell differentiation and mineralization through MAPK signaling pathways

Liang

et al. 2021

J of Periodontal Research

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Background and Objective Periodontal ligament stem cells (PDLSCs) are the primary cell source for the regeneration and remodeling of periodontal ligament (PDL). It is crucial to prevent PDLSCs from mineralization when using the PDLSCs for PDL regeneration. At present, little is known about how to inhibit PDLSC mineralization. This study investigates the effects of pyrophosphate (PPi) on inhibiting PDLSC osteogenic differentiation and mineralization as well as the underlying mechanism. Materials and Methods Human PDLSCs were cultured in an osteogenic differentiation medium with different PPi concentrations (0, 10, or 100 μM). The effects of PPi on osteogenic differentiation were assessed by ALP activity and the expressions of osteogenic related proteins (OPN, RUNX2, OSX, and DMP1). The mineralization formation was detected by alizarin red staining. The activation of MAPK signaling pathways (ERK1/2, JNK, and p38) was determined by western blotting and pathway blockade assays. The gene expressions of PPi's regulators (Ank, Enpp1, and Alpl) were assessed by real‐time PCR. Results Both low and high concentrations (10 μM and 100 μM) of PPi inhibited the mineralization of PDLSCs. The addition of PPi (10 μM or 100 μM) decreased the ALP activity of the PDLSCs to approximately two‐thirds of the control group on day 3. PPi reduced the expressions of RUNX2, OSX, and DMP1 on days 7, 14, and 21, while it increased the expression of OPN at the three time points. PPi enhanced the phosphorylation of MAPK pathways, and the application of corresponding MAPK pathway inhibitors reversed the osteogenic inhibition effects of PPi. Conclusion PPi inhibits the osteogenic differentiation and mineralization of PDLSCs in vitro through activating ERK1/2, JNK, and p38 signaling pathways.

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Progranulin promotes osteogenic differentiation of human periodontal ligament stem cells via tumor necrosis factor receptors to inhibit TNF‐α sensitized NF‐kB and activate ERK/JNK signaling

Cited by 19 publications

References 37 publications

Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol

Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol

miR-23b mediates TNF-α-Inhibited Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Targeting Runx2

Pyrophosphate inhibits periodontal ligament stem cell differentiation and mineralization through MAPK signaling pathways

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