The Experts below are selected from a list of 1425 Experts worldwide ranked by ideXlab platform
Martha J. Somerman - One of the best experts on this subject based on the ideXlab platform.
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Cementoblasts express pyrophosphate regulators in a time and space restricted manner.
2013Co-Authors: Brian L. Foster, Kanako J. Nagatomo, Francisco Humberto Nociti, Hanson Fong, Daisy Dunn, Anne B. Tran, Wei Wang, Sonoko Narisawa, Jose Luis Millán, Martha J. SomermanAbstract:TNAP was expressed strongly in all the periodontal tissues in (A) Ank; Enpp1+/+ control as well as both (B, C) Ank and Enpp1−/− models. Loss of ANK or NPP1 did not alter cementoblast TNAP expression. ANK was localized selectively to Cementoblasts in (D) control, and was increased when (F) Enpp1 was ablated. Like ANK, NPP1 was found at selectively greater concentrations in Cementoblasts in (G) controls, and was increased upon (H) Ank−/−. Specificity of antibody staining was confirmed in null mice in (E) and (I). All panels are mandibular first molar teeth at 26 dpn. Abbreviations: d = dentin; c = acellular cementum; p = periodontal ligament; b = bone. Cervical cementum is indicated by opposing black arrows. Scale bar = 100 µm.
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wnt β catenin pathway regulates bone morphogenetic protein bmp2 mediated differentiation of dental follicle cells
Journal of Periodontal Research, 2012Co-Authors: Karina Gonzales Silverio, Brian L. Foster, Martha J. Somerman, Francisco Humberto Nociti, Kathryn C Davidson, Richard G James, Allison M Adams, Randall T MoonAbstract:Silverio KG, Davidson KC, James RG, Adams AM, Foster BL, Nociti FH Jr, Somerman MJ, Moon RT. Wnt/β-catenin pathway regulates bone morphogenetic protein (BMP2)-mediated differentiation of dental follicle cells. J Periodont Res 2012; 47: 309–319. © 2011 John Wiley & Sons A/S Background and Objective: Bone morphogenetic protein 2 (BMP2)-induced osteogenic differentiation has been shown to occur through the canonical Wnt/βcatenin pathway, whereas factors promoting canonical Wnt signaling in Cementoblasts inhibit cell differentiation and promote cell proliferation in vitro. The aim of this study was to investigate whether putative precursor cells of Cementoblasts, dental follicle cells (murine SVF4 cells), when stimulated with BMP2, would exhibit changes in genes/proteins associated with the Wnt/β-catenin pathway. Material and Methods: SVF4 cells were stimulated with BMP2, and the following assays were carried out: (i) Wnt/β-catenin pathway activation assessed by western blotting, β-catenin/transcription factor (TCF) reporter assays and expression of the lymphoid enhancer-binding factor-1 (Lef1), transcription factor 7 (Tcf 7), Wnt inhibitor factor 1 (Wif1) and Axin2 (Axin2) genes; and (ii) cementoblast/osteoblast differentiation assessed by mineralization in vitro, and by the mRNA levels of runt-related transcription factor 2 (Runx2), osterix (Osx), alkaline phosphatase (Alp), osteocalcin (Ocn) and bone sialoprotein (Bsp), determined by quantitative PCR after treatment with wingless-type MMTV integration site family, member 3A (WNT3A) and knockdown of β-catenin. Results: WNT3A induced β-catenin nuclear translocation and up-regulated the transcriptional activity of a canonical Wnt-responsive reporter, suggesting that the Wnt/β-catenin pathway functions in SVF4 cells. Activation of Wnt signaling with WNT3A suppressed BMP2-mediated induction of cementoblast/osteoblast maturation of SVF4 cells. However, β-catenin knockdown showed that the BMP2-induced expression of cementoblast/osteoblast differentiation markers requires endogenous β-catenin. WNT3A down-regulated transcripts for Runx2, Alp and Ocn in SVF4 cells compared with untreated cells. In contrast, BMP2 induction of Bsp transcripts occurred independently of Wnt/β-catenin signaling. Conclusion: These data suggest that stabilization of β-catenin by WNT3A inhibits BMP2-mediated induction of cementoblast/osteoblast differentiation in SVF4 cells, although BMP2 requires endogenous Wnt/β-catenin signaling to promote cell maturation.
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bone morphogenetic protein 7 enhances cementoblast function in vitro
Journal of Periodontology, 2010Co-Authors: Sema S. Hakki, Brian L. Foster, Martha J. Somerman, Kanako J. Nagatomo, Erdogan E. Hakki, Buket S Bozkurt, Rahime M. NohutcuAbstract:Background: Bone morphogenetic protein (BMP)-7 is a potent bone-inducing factor and was shown to promote periodontal regeneration in vivo and in vitro; however, to our knowledge, the specific effect of BMP-7 on Cementoblasts has not been defined. We aimed to investigate the effects of BMP-7 on Cementoblasts, which are cells responsible for tooth root–cementum formation. We hypothesized that BMP-7 would regulate mineralized tissue–associated genes in Cementoblasts and influence the expression profile of genes associated with cementoblast extracellular matrix (ECM) and cell adhesion molecules (CAMs).Methods: A murine immortalized cementoblast cell line (OCCM.30) was cultured with and without 50 ng/ml BMP-7. After 72 hours, total RNA was isolated, and mRNA levels for bone/cementum markers, including bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor-2 (Runx2), were investigated by real-time quantitative reverse transcription-polymerase chain reaction (Q-PCR)....
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Bone Morphogenetic Protein‐7 Enhances Cementoblast Function In Vitro
Journal of periodontology, 2010Co-Authors: Sema S. Hakki, Brian L. Foster, Martha J. Somerman, Kanako J. Nagatomo, S. Buket Bozkurt, Erdogan E. Hakki, Rahime M. NohutcuAbstract:Background: Bone morphogenetic protein (BMP)-7 is a potent bone-inducing factor and was shown to promote periodontal regeneration in vivo and in vitro; however, to our knowledge, the specific effect of BMP-7 on Cementoblasts has not been defined. We aimed to investigate the effects of BMP-7 on Cementoblasts, which are cells responsible for tooth root–cementum formation. We hypothesized that BMP-7 would regulate mineralized tissue–associated genes in Cementoblasts and influence the expression profile of genes associated with cementoblast extracellular matrix (ECM) and cell adhesion molecules (CAMs).Methods: A murine immortalized cementoblast cell line (OCCM.30) was cultured with and without 50 ng/ml BMP-7. After 72 hours, total RNA was isolated, and mRNA levels for bone/cementum markers, including bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor-2 (Runx2), were investigated by real-time quantitative reverse transcription-polymerase chain reaction (Q-PCR)....
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wnt signaling inhibits cementoblast differentiation
2010Co-Authors: Eiji Nemoto, Martha J. Somerman, Yohei Koshikawa, Sousuke Kanaya, Masahiro Tsuchiya, Masato Tamura, Hidetoshi ShimauchiAbstract:Wnt signaling has been implicated in increased bone formation by controlling mesenchymal stem cell or osteoblastic cell functions; however the role of Wnt signaling on cementogenesis has not been examined. Exposure to Wnt3a inhibited the expression of the osteocalcin (OCN) gene. This effect was accompanied by decreased gene expression of Runx2. Pretreatment with Dickkopf-1 attenuated the suppressive effects of Wnt3a on mRNA expression of Runx2 and OCN on Cementoblasts. These findings suggest that canonical Wnt signaling inhibits cementoblast differentiation via regulation of expression of Runx2. Elucidating the role of Wnt in controlling cementoblast function will provide new tools needed to improve on existing periodontal regeneration therapies.
Zhengguo Cao - One of the best experts on this subject based on the ideXlab platform.
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Irisin promotes cementoblast differentiation via p38 MAPK pathway
Oral diseases, 2020Co-Authors: Jiaqi Zhu, Zhengguo Cao, Yunlong Wang, Yunru Hao, Jiawen PanAbstract:Irisin is a newly identified exercise-induced myokine which can affect glucose metabolism and cortical bone mass and strength. However, the influence of irisin on Cementoblasts remains largely unknown. An immortalized mouse cementoblast cell line OCCM-30 was used in this study. Cementoblast differentiation markers and PGC-1α in cells cultured with mineral induction medium were evaluated by qRT-PCR. Cementoblast mineralization was evaluated by alizarin red staining. Differentiation markers and the activity of p38 MAPK pathway under irisin stimulation were assessed by qRT-PCR or Western blot analysis. p38 MAPK pathway inhibitor SB203580 or p38 siRNA was used to further identify the regulatory mechanism. Cell proliferation treated with irisin was examined by CCK-8 method. The expression of Runx2, osterix, ALP, and PGC-1α was up-regulated consistently under mineral induction. The formation of mineralized nodules was increased by irisin. Runx2, osterix, ALP, and osteocalcin were obviously up-regulated under irisin stimulation as well as the activity of p38 MAPK pathway. When pretreated with SB203580 or p38 siRNA before irisin stimulation, the irisin-induced differentiation was distinctly suppressed. OCCM-30 cell proliferation was enhanced when treated with high-dose irisin for long time. Irisin can promote the differentiation of Cementoblasts via p38 MAPK pathway. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.
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irisin promotes cementoblast differentiation via p38 mapk pathway
Oral Diseases, 2020Co-Authors: Jiaqi Zhu, Zhengguo Cao, Yunlong Wang, Yunru Hao, Jiawen PanAbstract:Objective Irisin is a newly identified exercise-induced myokine which can affect glucose metabolism and cortical bone mass and strength. However, the influence of irisin on Cementoblasts remains largely unknown. Material and methods An immortalized mouse cementoblast cell line OCCM-30 was used in this study. Cementoblast differentiation markers and PGC-1α in cells cultured with mineral induction medium were evaluated by qRT-PCR. Cementoblast mineralization was evaluated by alizarin red staining. Differentiation markers and the activity of p38 MAPK pathway under irisin stimulation were assessed by qRT-PCR or Western blot analysis. p38 MAPK pathway inhibitor SB203580 or p38 siRNA was used to further identify the regulatory mechanism. Cell proliferation treated with irisin was examined by CCK-8 method. Results The expression of Runx2, osterix, ALP, and PGC-1α was up-regulated consistently under mineral induction. The formation of mineralized nodules was increased by irisin. Runx2, osterix, ALP, and osteocalcin were obviously up-regulated under irisin stimulation as well as the activity of p38 MAPK pathway. When pretreated with SB203580 or p38 siRNA before irisin stimulation, the irisin-induced differentiation was distinctly suppressed. OCCM-30 cell proliferation was enhanced when treated with high-dose irisin for long time. Conclusion Irisin can promote the differentiation of Cementoblasts via p38 MAPK pathway.
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microrna 181b 5p modulates tumor necrosis factor α induced inflammatory responses by targeting interleukin 6 in Cementoblasts
Journal of Cellular Physiology, 2019Co-Authors: Xiaoxuan Wang, Chenxi Jiang, Haiqing Liao, Junbo Xiang, Hualing Sun, Huan Liu, Zhengguo CaoAbstract:Tooth cementum is a bone-like mineralized tissue and serves as a microbial barrier against invasion and destruction. Cementum is also responsible for tooth stability and defending pulp from outside stimuli, which is formed by Cementoblasts. Although it is crucial for periodontal and periapical diseases, the mechanisms underlying the pathophysiological changes of Cementoblasts and their inflammatory responses remain unclear. MiR-181b is found to modulate vascular inflammation and endotoxin tolerance. In this study, miR-181b-5p was downregulated in tumor necrosis factor-α (TNF-α)-stimulated Cementoblasts, whereas proinflammatory molecules increased. The mouse periapical lesions have similar results, which imitate an inflammatory environment for Cementoblasts in vivo. The bioinformatics analysis and dual luciferase reporter assay suggested that miR-181b-5p targeted interleukin-6 (IL-6). Overexpressing miR-181b-5p negatively regulated IL-6 and proinflammatory chemokine. Western blot analysis and luciferase activity reporter assay verified that miR-181b-5p weakened the NF-κB activity. Hence, miR-181b-5p moderated proinflammatory chemokine production by targeting IL-6 in Cementoblasts and NF-κB signaling pathway was involved. Furthermore, miR-181b-5p promoted cementoblast apoptosis, which may enhance the resolution of inflammation. Overall, our data revealed that miR-181b-5p was a negative regulator of TNF-α-induced inflammatory responses in Cementoblasts.
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MiR-361-3p/Nfat5 Signaling Axis Controls Cementoblast Differentiation:
Journal of dental research, 2019Co-Authors: Haiqing Liao, Chenxi Jiang, H Liu, H. Sun, Xiaoxuan Wang, Junbo Xiang, Zhengguo CaoAbstract:The development of periodontal tissue is a complex process, including cementoblast proliferation and differentiation. Emerging reports suggest that microRNAs (miRNAs) play crucial roles in gene regulatory networks governing numerous biological processes. However, how miRNAs modulate cementoblast proliferation and differentiation remains largely unknown. In a previous study, we performed miRNA microarray profiling to fully reveal the expression patterns of miRNAs involved in cementoblast differentiation. We focused on miR-361-3p, which decreased during cementoblast differentiation. Overexpression of miR-361-3p resulted in decreased cementoblast differentiation, whereas the functional inhibition of miR-361-3p yielded the opposite effect. The bioinformatics approach identified nuclear factor of activated T-cell 5 (Nfat5) as a potential target of miR-361-3p, which was further verified by dual luciferase assay. Meanwhile, the expression pattern of Nfat5 was verified both in vitro and in vivo. Furthermore, knockdown of Nfat5 mimicked the inhibitory effect of overexpressing miR-361-3p in Cementoblasts. Moreover, multiple signaling pathways, including the Erk1/2, JNK, p38, PI3K-Akt, and NF-κB pathways, were notably activated, and the Wnt/s-catenin pathway was blocked by downregulation of Nfat5 or forced expression of miR-361-3p in cementoblast differentiation. Finally, the complementary approach demonstrated that miR-361-3p regulated cementoblast differentiation via or partially via Erk1/2 and PI3K-Akt. Overall, our study elucidated that the JNK, p38, NF-κB, and Wnt/s-catenin pathways act as balancing players in the miR-361-3p/Nfat5 signaling axis during cementoblast differentiation.
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CXXC5 Mediates P. gingivalis-suppressed Cementoblast Functions Partially via MAPK Signaling Network.
International journal of biological sciences, 2019Co-Authors: Xiaoxuan Wang, Chenxi Jiang, H Liu, Haiqing Liao, Yi Guo, Zhengguo CaoAbstract:Porphyromonas (P.) gingivalis associates tightly with periodontal diseases and it is also a dominant pathogen of periapical periodontitis. However, the influence of P. gingivalis on Cementoblasts, root surface cells pivotal in the apical areas, and the possible involvement of other molecules remain largely elusive. CXXC5 is a nuclear protein that regulates gene expression as well as cell growth, differentiation, and apoptosis. In this study, P. gingivalis repressed the mineralization capacity of Cementoblasts by inducing inflammatory reactions and inhibiting cell differentiation. Intriguingly, the expression of CXXC5 decreased in P. gingivalis-treated OCCM-30 cells and apical periodontitis models but gradually increased during mineralization. Furthermore, RNA interference of CXXC5 significantly inhibited cementoblast differentiation, represented by decline of bone-associated markers Osterix, osteocalcin (OCN), and alkaline phosphatase (ALP). CXXC5 overexpression facilitated differentiation, and therefore attenuated the P. gingivalis-repressed effects on OCCM-30 cells. In addition, Erk1/2, p38, and PI3K-Akt were inactivated by silencing CXXC5 and activated upon its overexpression, whereas Wnt/β-catenin exhibited an opposite trend. The employment of specific inhibitors revealed that the CXXC5-dependent promotions of cementoblast differentiation were partially abrogated by p38 and PI3K-Akt inhibitors but were exacerbated by inhibiting Erk1/2. Overall, our experiment demonstrated a novel function of CXXC5 in the regeneration of impaired cementum caused by P. gingivalis invasion and suggested that MAPK signaling network balances the facilitation effects of CXXC5 in cementoblast differentiation.
Weixiong Xiao - One of the best experts on this subject based on the ideXlab platform.
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Article Multi-Walled Carbon Nanotubes Promote Cementoblast Differentiation and Mineralization through the TGF-β/Smad Signaling Pathway
2016Co-Authors: Zhimin Zhu, Weixiong XiaoAbstract:Abstract: Excretion of cementum by Cementoblasts on the root surface is a process indispensable for the formation of a functional periodontal ligament. This study investigated whether carboxyl group-functionalized multi-walled carbon nanotubes (MWCNT-COOH) could enhance differentiation and mineralization of mammalian Cementoblasts (OCCM-30) and the possible signaling pathway involved in this process. Cementoblasts were incubated with various doses of MWCNT-COOH suspension. Cell viability was detected, and a scanning electron microscopy (SEM) observed both the nanomaterials and the growth of cells cultured with the materials. Alizarin red staining was used to investigate the formation of calcium deposits. Real-time PCR and western blot were used to detect cementoblast differentiation and the underlying mechanisms through the expression of the osteogenic genes and the downstream effectors of the TGF-β/Smad signaling. The results showed that 5 µg/mL MWCNT-COOH had the most obvious effects on promoting differentiation without significant toxicity. Alp, Ocn, Bsp, Opn, Col1 and Runx2 gene expression was up-regulated. Smad2 and Smad3 mRNA was up-regulated, while Smad7 was first down-regulated on Day 3 and later up-regulated on Day 7. The elevated level
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Multi-walled carbon nanotubes promote cementoblast differentiation and mineralization through the TGF-β/Smad signaling pathway.
International journal of molecular sciences, 2015Co-Authors: Zhimin Zhu, Weixiong XiaoAbstract:Excretion of cementum by Cementoblasts on the root surface is a process indispensable for the formation of a functional periodontal ligament. This study investigated whether carboxyl group-functionalized multi-walled carbon nanotubes (MWCNT-COOH) could enhance differentiation and mineralization of mammalian Cementoblasts (OCCM-30) and the possible signaling pathway involved in this process. Cementoblasts were incubated with various doses of MWCNT-COOH suspension. Cell viability was detected, and a scanning electron microscopy (SEM) observed both the nanomaterials and the growth of cells cultured with the materials. Alizarin red staining was used to investigate the formation of calcium deposits. Real-time PCR and western blot were used to detect cementoblast differentiation and the underlying mechanisms through the expression of the osteogenic genes and the downstream effectors of the TGF-β/Smad signaling. The results showed that 5 µg/mL MWCNT-COOH had the most obvious effects on promoting differentiation without significant toxicity. Alp, Ocn, Bsp, Opn, Col1 and Runx2 gene expression was up-regulated. Smad2 and Smad3 mRNA was up-regulated, while Smad7 was first down-regulated on Day 3 and later up-regulated on Day 7. The elevated levels of phospho-Smad2/3 were also confirmed by western blot. In sum, the MWCNT-COOH promoted cementoblast differentiation and mineralization, at least partially, through interactions with the TGF-β/Smad pathway.
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multi walled carbon nanotubes promote cementoblast differentiation and mineralization through the tgf β smad signaling pathway
International Journal of Molecular Sciences, 2015Co-Authors: Zhimin Zhu, Weixiong XiaoAbstract:Excretion of cementum by Cementoblasts on the root surface is a process indispensable for the formation of a functional periodontal ligament. This study investigated whether carboxyl group-functionalized multi-walled carbon nanotubes (MWCNT-COOH) could enhance differentiation and mineralization of mammalian Cementoblasts (OCCM-30) and the possible signaling pathway involved in this process. Cementoblasts were incubated with various doses of MWCNT-COOH suspension. Cell viability was detected, and a scanning electron microscopy (SEM) observed both the nanomaterials and the growth of cells cultured with the materials. Alizarin red staining was used to investigate the formation of calcium deposits. Real-time PCR and western blot were used to detect cementoblast differentiation and the underlying mechanisms through the expression of the osteogenic genes and the downstream effectors of the TGF-β/Smad signaling. The results showed that 5 µg/mL MWCNT-COOH had the most obvious effects on promoting differentiation without significant toxicity. Alp, Ocn, Bsp, Opn, Col1 and Runx2 gene expression was up-regulated. Smad2 and Smad3 mRNA was up-regulated, while Smad7 was first down-regulated on Day 3 and later up-regulated on Day 7. The elevated levels of phospho-Smad2/3 were also confirmed by western blot. In sum, the MWCNT-COOH promoted cementoblast differentiation and mineralization, at least partially, through interactions with the TGF-β/Smad pathway.
Chenxi Jiang - One of the best experts on this subject based on the ideXlab platform.
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microrna 181b 5p modulates tumor necrosis factor α induced inflammatory responses by targeting interleukin 6 in Cementoblasts
Journal of Cellular Physiology, 2019Co-Authors: Xiaoxuan Wang, Chenxi Jiang, Haiqing Liao, Junbo Xiang, Hualing Sun, Huan Liu, Zhengguo CaoAbstract:Tooth cementum is a bone-like mineralized tissue and serves as a microbial barrier against invasion and destruction. Cementum is also responsible for tooth stability and defending pulp from outside stimuli, which is formed by Cementoblasts. Although it is crucial for periodontal and periapical diseases, the mechanisms underlying the pathophysiological changes of Cementoblasts and their inflammatory responses remain unclear. MiR-181b is found to modulate vascular inflammation and endotoxin tolerance. In this study, miR-181b-5p was downregulated in tumor necrosis factor-α (TNF-α)-stimulated Cementoblasts, whereas proinflammatory molecules increased. The mouse periapical lesions have similar results, which imitate an inflammatory environment for Cementoblasts in vivo. The bioinformatics analysis and dual luciferase reporter assay suggested that miR-181b-5p targeted interleukin-6 (IL-6). Overexpressing miR-181b-5p negatively regulated IL-6 and proinflammatory chemokine. Western blot analysis and luciferase activity reporter assay verified that miR-181b-5p weakened the NF-κB activity. Hence, miR-181b-5p moderated proinflammatory chemokine production by targeting IL-6 in Cementoblasts and NF-κB signaling pathway was involved. Furthermore, miR-181b-5p promoted cementoblast apoptosis, which may enhance the resolution of inflammation. Overall, our data revealed that miR-181b-5p was a negative regulator of TNF-α-induced inflammatory responses in Cementoblasts.
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MiR-361-3p/Nfat5 Signaling Axis Controls Cementoblast Differentiation:
Journal of dental research, 2019Co-Authors: Haiqing Liao, Chenxi Jiang, H Liu, H. Sun, Xiaoxuan Wang, Junbo Xiang, Zhengguo CaoAbstract:The development of periodontal tissue is a complex process, including cementoblast proliferation and differentiation. Emerging reports suggest that microRNAs (miRNAs) play crucial roles in gene regulatory networks governing numerous biological processes. However, how miRNAs modulate cementoblast proliferation and differentiation remains largely unknown. In a previous study, we performed miRNA microarray profiling to fully reveal the expression patterns of miRNAs involved in cementoblast differentiation. We focused on miR-361-3p, which decreased during cementoblast differentiation. Overexpression of miR-361-3p resulted in decreased cementoblast differentiation, whereas the functional inhibition of miR-361-3p yielded the opposite effect. The bioinformatics approach identified nuclear factor of activated T-cell 5 (Nfat5) as a potential target of miR-361-3p, which was further verified by dual luciferase assay. Meanwhile, the expression pattern of Nfat5 was verified both in vitro and in vivo. Furthermore, knockdown of Nfat5 mimicked the inhibitory effect of overexpressing miR-361-3p in Cementoblasts. Moreover, multiple signaling pathways, including the Erk1/2, JNK, p38, PI3K-Akt, and NF-κB pathways, were notably activated, and the Wnt/s-catenin pathway was blocked by downregulation of Nfat5 or forced expression of miR-361-3p in cementoblast differentiation. Finally, the complementary approach demonstrated that miR-361-3p regulated cementoblast differentiation via or partially via Erk1/2 and PI3K-Akt. Overall, our study elucidated that the JNK, p38, NF-κB, and Wnt/s-catenin pathways act as balancing players in the miR-361-3p/Nfat5 signaling axis during cementoblast differentiation.
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CXXC5 Mediates P. gingivalis-suppressed Cementoblast Functions Partially via MAPK Signaling Network.
International journal of biological sciences, 2019Co-Authors: Xiaoxuan Wang, Chenxi Jiang, H Liu, Haiqing Liao, Yi Guo, Zhengguo CaoAbstract:Porphyromonas (P.) gingivalis associates tightly with periodontal diseases and it is also a dominant pathogen of periapical periodontitis. However, the influence of P. gingivalis on Cementoblasts, root surface cells pivotal in the apical areas, and the possible involvement of other molecules remain largely elusive. CXXC5 is a nuclear protein that regulates gene expression as well as cell growth, differentiation, and apoptosis. In this study, P. gingivalis repressed the mineralization capacity of Cementoblasts by inducing inflammatory reactions and inhibiting cell differentiation. Intriguingly, the expression of CXXC5 decreased in P. gingivalis-treated OCCM-30 cells and apical periodontitis models but gradually increased during mineralization. Furthermore, RNA interference of CXXC5 significantly inhibited cementoblast differentiation, represented by decline of bone-associated markers Osterix, osteocalcin (OCN), and alkaline phosphatase (ALP). CXXC5 overexpression facilitated differentiation, and therefore attenuated the P. gingivalis-repressed effects on OCCM-30 cells. In addition, Erk1/2, p38, and PI3K-Akt were inactivated by silencing CXXC5 and activated upon its overexpression, whereas Wnt/β-catenin exhibited an opposite trend. The employment of specific inhibitors revealed that the CXXC5-dependent promotions of cementoblast differentiation were partially abrogated by p38 and PI3K-Akt inhibitors but were exacerbated by inhibiting Erk1/2. Overall, our experiment demonstrated a novel function of CXXC5 in the regeneration of impaired cementum caused by P. gingivalis invasion and suggested that MAPK signaling network balances the facilitation effects of CXXC5 in cementoblast differentiation.
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MicroRNA‐181b‐5p modulates tumor necrosis factor‐α‐induced inflammatory responses by targeting interleukin‐6 in Cementoblasts
Journal of cellular physiology, 2019Co-Authors: Xiaoxuan Wang, Chenxi Jiang, Haiqing Liao, Junbo Xiang, Hualing Sun, Huan Liu, Zhengguo CaoAbstract:Tooth cementum is a bone-like mineralized tissue and serves as a microbial barrier against invasion and destruction. Cementum is also responsible for tooth stability and defending pulp from outside stimuli, which is formed by Cementoblasts. Although it is crucial for periodontal and periapical diseases, the mechanisms underlying the pathophysiological changes of Cementoblasts and their inflammatory responses remain unclear. MiR-181b is found to modulate vascular inflammation and endotoxin tolerance. In this study, miR-181b-5p was downregulated in tumor necrosis factor-α (TNF-α)-stimulated Cementoblasts, whereas proinflammatory molecules increased. The mouse periapical lesions have similar results, which imitate an inflammatory environment for Cementoblasts in vivo. The bioinformatics analysis and dual luciferase reporter assay suggested that miR-181b-5p targeted interleukin-6 (IL-6). Overexpressing miR-181b-5p negatively regulated IL-6 and proinflammatory chemokine. Western blot analysis and luciferase activity reporter assay verified that miR-181b-5p weakened the NF-κB activity. Hence, miR-181b-5p moderated proinflammatory chemokine production by targeting IL-6 in Cementoblasts and NF-κB signaling pathway was involved. Furthermore, miR-181b-5p promoted cementoblast apoptosis, which may enhance the resolution of inflammation. Overall, our data revealed that miR-181b-5p was a negative regulator of TNF-α-induced inflammatory responses in Cementoblasts.
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Downregulation of angiopoietin-like protein 2 inhibits cementoblast differentiation partially by activating the ERK1/2 signaling pathway.
American journal of translational research, 2019Co-Authors: Chenxi Jiang, H Liu, H. Sun, Xiaoxuan Wang, Haiqing Liao, Zhengguo CaoAbstract:Angiopoietin-like protein 2 (ANGPTL2) is abundantly expressed in adipose tissue, is associated with tissue homeostasis, and promotes osteoblast and chondrocyte differentiation. In teeth, cementum, a thin layer of mineralized tissue that is formed by Cementoblasts, covers the entire root surface and is a vital component of periodontium. The Cementoblasts regulate the deposition and mineralization of the cementum matrix. However, the effects of ANGPTL2 on cementoblast differentiation have not been studied. The objective of this study was to elucidate the role of ANGPTL2 during cementoblast differentiation and determine its underlying mechanisms. Our results showed that the expression levels of ANGPTL2 gradually increased during cementoblast differentiation. After ANGPTL2 was knocked down using short-hairpin RNA, the levels of the osteogenic markers osterix (OSX), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN) decreased. In addition, ALP activity and the number of calcified nodules were dramatically reduced compared with those in the negative control. Interestingly, the ERK1/2 signaling pathway was activated after ANGPTL2 knockdown. Treatment with PD98059, the inhibitor of the ERK1/2 signaling pathway, partially rescued the decreased differentiation capability of cementoblast caused by ANGPTL2 downregulation. Collectively, ANGPTL2 knockdown inhibited cementoblast differentiation partially by activating the ERK1/2 signaling pathway. These findings suggest that ANGPTL2 was indispensable in cementoblast differentiation.
Haiqing Liao - One of the best experts on this subject based on the ideXlab platform.
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microrna 181b 5p modulates tumor necrosis factor α induced inflammatory responses by targeting interleukin 6 in Cementoblasts
Journal of Cellular Physiology, 2019Co-Authors: Xiaoxuan Wang, Chenxi Jiang, Haiqing Liao, Junbo Xiang, Hualing Sun, Huan Liu, Zhengguo CaoAbstract:Tooth cementum is a bone-like mineralized tissue and serves as a microbial barrier against invasion and destruction. Cementum is also responsible for tooth stability and defending pulp from outside stimuli, which is formed by Cementoblasts. Although it is crucial for periodontal and periapical diseases, the mechanisms underlying the pathophysiological changes of Cementoblasts and their inflammatory responses remain unclear. MiR-181b is found to modulate vascular inflammation and endotoxin tolerance. In this study, miR-181b-5p was downregulated in tumor necrosis factor-α (TNF-α)-stimulated Cementoblasts, whereas proinflammatory molecules increased. The mouse periapical lesions have similar results, which imitate an inflammatory environment for Cementoblasts in vivo. The bioinformatics analysis and dual luciferase reporter assay suggested that miR-181b-5p targeted interleukin-6 (IL-6). Overexpressing miR-181b-5p negatively regulated IL-6 and proinflammatory chemokine. Western blot analysis and luciferase activity reporter assay verified that miR-181b-5p weakened the NF-κB activity. Hence, miR-181b-5p moderated proinflammatory chemokine production by targeting IL-6 in Cementoblasts and NF-κB signaling pathway was involved. Furthermore, miR-181b-5p promoted cementoblast apoptosis, which may enhance the resolution of inflammation. Overall, our data revealed that miR-181b-5p was a negative regulator of TNF-α-induced inflammatory responses in Cementoblasts.
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MiR-361-3p/Nfat5 Signaling Axis Controls Cementoblast Differentiation:
Journal of dental research, 2019Co-Authors: Haiqing Liao, Chenxi Jiang, H Liu, H. Sun, Xiaoxuan Wang, Junbo Xiang, Zhengguo CaoAbstract:The development of periodontal tissue is a complex process, including cementoblast proliferation and differentiation. Emerging reports suggest that microRNAs (miRNAs) play crucial roles in gene regulatory networks governing numerous biological processes. However, how miRNAs modulate cementoblast proliferation and differentiation remains largely unknown. In a previous study, we performed miRNA microarray profiling to fully reveal the expression patterns of miRNAs involved in cementoblast differentiation. We focused on miR-361-3p, which decreased during cementoblast differentiation. Overexpression of miR-361-3p resulted in decreased cementoblast differentiation, whereas the functional inhibition of miR-361-3p yielded the opposite effect. The bioinformatics approach identified nuclear factor of activated T-cell 5 (Nfat5) as a potential target of miR-361-3p, which was further verified by dual luciferase assay. Meanwhile, the expression pattern of Nfat5 was verified both in vitro and in vivo. Furthermore, knockdown of Nfat5 mimicked the inhibitory effect of overexpressing miR-361-3p in Cementoblasts. Moreover, multiple signaling pathways, including the Erk1/2, JNK, p38, PI3K-Akt, and NF-κB pathways, were notably activated, and the Wnt/s-catenin pathway was blocked by downregulation of Nfat5 or forced expression of miR-361-3p in cementoblast differentiation. Finally, the complementary approach demonstrated that miR-361-3p regulated cementoblast differentiation via or partially via Erk1/2 and PI3K-Akt. Overall, our study elucidated that the JNK, p38, NF-κB, and Wnt/s-catenin pathways act as balancing players in the miR-361-3p/Nfat5 signaling axis during cementoblast differentiation.
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CXXC5 Mediates P. gingivalis-suppressed Cementoblast Functions Partially via MAPK Signaling Network.
International journal of biological sciences, 2019Co-Authors: Xiaoxuan Wang, Chenxi Jiang, H Liu, Haiqing Liao, Yi Guo, Zhengguo CaoAbstract:Porphyromonas (P.) gingivalis associates tightly with periodontal diseases and it is also a dominant pathogen of periapical periodontitis. However, the influence of P. gingivalis on Cementoblasts, root surface cells pivotal in the apical areas, and the possible involvement of other molecules remain largely elusive. CXXC5 is a nuclear protein that regulates gene expression as well as cell growth, differentiation, and apoptosis. In this study, P. gingivalis repressed the mineralization capacity of Cementoblasts by inducing inflammatory reactions and inhibiting cell differentiation. Intriguingly, the expression of CXXC5 decreased in P. gingivalis-treated OCCM-30 cells and apical periodontitis models but gradually increased during mineralization. Furthermore, RNA interference of CXXC5 significantly inhibited cementoblast differentiation, represented by decline of bone-associated markers Osterix, osteocalcin (OCN), and alkaline phosphatase (ALP). CXXC5 overexpression facilitated differentiation, and therefore attenuated the P. gingivalis-repressed effects on OCCM-30 cells. In addition, Erk1/2, p38, and PI3K-Akt were inactivated by silencing CXXC5 and activated upon its overexpression, whereas Wnt/β-catenin exhibited an opposite trend. The employment of specific inhibitors revealed that the CXXC5-dependent promotions of cementoblast differentiation were partially abrogated by p38 and PI3K-Akt inhibitors but were exacerbated by inhibiting Erk1/2. Overall, our experiment demonstrated a novel function of CXXC5 in the regeneration of impaired cementum caused by P. gingivalis invasion and suggested that MAPK signaling network balances the facilitation effects of CXXC5 in cementoblast differentiation.
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MicroRNA‐181b‐5p modulates tumor necrosis factor‐α‐induced inflammatory responses by targeting interleukin‐6 in Cementoblasts
Journal of cellular physiology, 2019Co-Authors: Xiaoxuan Wang, Chenxi Jiang, Haiqing Liao, Junbo Xiang, Hualing Sun, Huan Liu, Zhengguo CaoAbstract:Tooth cementum is a bone-like mineralized tissue and serves as a microbial barrier against invasion and destruction. Cementum is also responsible for tooth stability and defending pulp from outside stimuli, which is formed by Cementoblasts. Although it is crucial for periodontal and periapical diseases, the mechanisms underlying the pathophysiological changes of Cementoblasts and their inflammatory responses remain unclear. MiR-181b is found to modulate vascular inflammation and endotoxin tolerance. In this study, miR-181b-5p was downregulated in tumor necrosis factor-α (TNF-α)-stimulated Cementoblasts, whereas proinflammatory molecules increased. The mouse periapical lesions have similar results, which imitate an inflammatory environment for Cementoblasts in vivo. The bioinformatics analysis and dual luciferase reporter assay suggested that miR-181b-5p targeted interleukin-6 (IL-6). Overexpressing miR-181b-5p negatively regulated IL-6 and proinflammatory chemokine. Western blot analysis and luciferase activity reporter assay verified that miR-181b-5p weakened the NF-κB activity. Hence, miR-181b-5p moderated proinflammatory chemokine production by targeting IL-6 in Cementoblasts and NF-κB signaling pathway was involved. Furthermore, miR-181b-5p promoted cementoblast apoptosis, which may enhance the resolution of inflammation. Overall, our data revealed that miR-181b-5p was a negative regulator of TNF-α-induced inflammatory responses in Cementoblasts.
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Downregulation of angiopoietin-like protein 2 inhibits cementoblast differentiation partially by activating the ERK1/2 signaling pathway.
American journal of translational research, 2019Co-Authors: Chenxi Jiang, H Liu, H. Sun, Xiaoxuan Wang, Haiqing Liao, Zhengguo CaoAbstract:Angiopoietin-like protein 2 (ANGPTL2) is abundantly expressed in adipose tissue, is associated with tissue homeostasis, and promotes osteoblast and chondrocyte differentiation. In teeth, cementum, a thin layer of mineralized tissue that is formed by Cementoblasts, covers the entire root surface and is a vital component of periodontium. The Cementoblasts regulate the deposition and mineralization of the cementum matrix. However, the effects of ANGPTL2 on cementoblast differentiation have not been studied. The objective of this study was to elucidate the role of ANGPTL2 during cementoblast differentiation and determine its underlying mechanisms. Our results showed that the expression levels of ANGPTL2 gradually increased during cementoblast differentiation. After ANGPTL2 was knocked down using short-hairpin RNA, the levels of the osteogenic markers osterix (OSX), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN) decreased. In addition, ALP activity and the number of calcified nodules were dramatically reduced compared with those in the negative control. Interestingly, the ERK1/2 signaling pathway was activated after ANGPTL2 knockdown. Treatment with PD98059, the inhibitor of the ERK1/2 signaling pathway, partially rescued the decreased differentiation capability of cementoblast caused by ANGPTL2 downregulation. Collectively, ANGPTL2 knockdown inhibited cementoblast differentiation partially by activating the ERK1/2 signaling pathway. These findings suggest that ANGPTL2 was indispensable in cementoblast differentiation.