Calcium-sensing receptor-ERK signaling promotes odontoblastic differentiation of human dental pulp cells

Mizumachi, Hiroyuki; Yoshida, Shinichiro; Tomokiyo, Atsushi; Hasegawa, Daigaku; Hamano, Sayuri; Yuda, Atsushi; Sugii, Hideki; Serita, S.; Mitarai, Hiromi; Koori, Katsuaki; Wada, Naohisa; Maeda, Hidefumi

doi:10.1016/j.bone.2017.05.012

Cited by 40 publications

(37 citation statements)

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“…We recently showed that DM promoted odontoblastic differentiation of HDPCs (Mizumachi et al, ; Serita et al, ). To examine the effects of TNF‐α on the odontoblastic differentiation of yHDPCs and sHDPCs, the cells were cultured in CM or DM with or without TNF‐α for 7 days.…”

Section: Resultsmentioning

confidence: 99%

Senescence and odontoblastic differentiation of dental pulp cells

Nozu

Tomokiyo

Hasegawa

et al. 2018

Journal Cellular Physiology

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Cellular senescence has been suggested to be involved in physiological changes of cytokine production. Previous studies showed that the concentration of tumor necrosis factor-α (TNF-α) is higher in the blood of aged people compared with that of young people. So far, the precise effects of TNF-α on the odontoblastic differentiation of pulp cells have been controversial. Therefore, we aimed to clarify how this cytokine affected pulp cells during aging. Human dental pulp cells (HDPCs) were cultured until reaching the plateau of their growth, and the cells were isolated at actively (young HDPCs; yHDPCs) or inactively (senescent HDPCs; sHDPCs) proliferating stages. sHDPCs expressed senescence-related molecules while yHDPCs did not. When these HDPCs were cultured in an odontoblast-inductive medium, both young and senescent cells showed mineralization, but mineralization in sHDPCs was lower compared with yHDPCs. However, the administration of TNF-α to this culture medium altered these responses: yHDPCs showed downregulated mineralization, while sHDPCs exhibited significantly increased mineralization. Furthermore, the expression of tumor necrosis factor receptor 1 (TNFR1), a receptor of TNF-α, was significantly upregulated in sHDPCs compared with yHDPCs. Downregulation of TNFR1 expression led to decreased mineralization of TNF-α-treated sHDPCs, whereas restored the reduction in TNF-α-treated yHDPCs. These results suggested that sHDPCs preserved the odontoblastic differentiation capacity and TNF-α promoted odontoblastic differentiation of HDPCs with the progress of their population doublings through increased expression of TNFR1. Thus, TNF-α might exert a different effect on the odontoblastic differentiation of HDPCs depending on their proliferating activity. In addition, the calcification of pulp chamber with age may be related with increased reactivity of pulp cells to TNF-α.

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Section: Resultsmentioning

confidence: 99%

Senescence and odontoblastic differentiation of dental pulp cells

Nozu

Tomokiyo

Hasegawa

et al. 2018

Journal Cellular Physiology

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“…The addition of MTA to culture medium increased the concentration of Ca 2+ by ~0.3 mM after 2 hr (Takita et al, ) and significantly enhanced the mRNA expression and protein production of BMP‐2 in human DPCs, indicating the important role played by BMP‐2 in osteo/odontoblastic differentiation stimulated by MTA (Rodrigues et al, ; Yasuda, Ogawa, Arakawa, Kadowaki, & Saito, ). Subsequent studies have revealed that the mechanisms of MTA‐induced osteo/odontoblastic differentiation are similar to those observed in CaCl 2 ‐treated cells, that is, in the MAPK signaling pathway (upon ERK, p38, and c‐Jun N‐terminal kinase [JNK] activation), MTA induced osteo/odontoblastic differentiation of human DPCs (Mizumachi et al, ; Woo et al, ; Zhao et al, ). Interestingly, ERK and JNK phosphorylation can be inhibited by nifedipine, an L‐type Ca 2+ channel blocker (Woo et al, ), but no inhibitory effect of nifedipine was observed in p38 phosphorylation, suggesting that Ca 2+ influx through L‐type Ca 2+ channels is required for the selective activation of ERK and seems to operate independently of p38 signaling (Mulvaney, Zhang, Fewtrell, & Roberson, ; Tada et al, ).…”

Section: Cellular Responses To Extracellular Ca2+ and The Signaling Pmentioning

confidence: 85%

“…MTA and MTA‐like materials have been continuously introduced since the mid‐1990s and have been used clinically with success rates similar or superior to those achieved using Ca(OH) 2 (Komabayashi, Zhu, Eberhart, & Imai, ; Z. Li, Cao, Fan, & Xu, ). These improvements may be, in part, due to osteo/odontogenic differentiation of human DPCs induced by the higher levels of Ca 2+ released from MTA (Dudeja, Kumari, Singh, & Taneja, ) and mobilization of Ca 2+ , silicon, and strontium ions via the activation of Ca 2+ channels (e.g., CaSR) and MAPK pathways (J. M. Kim et al, ; Mizumachi et al, ; Wu et al, ). Furthermore, H. Zhang, Shen, Ruse, and Haapasalo () attributed the high antimicrobial activity of iRoot SP (an MTA‐like material) to its active release of Ca 2+ and its high pH and hydrophilicity.…”

Section: Clinical Significance: Ca2+ Signaling As a Therapeutic Targementioning

confidence: 99%

“…Interestingly, ERK and JNK phosphorylation can be inhibited by nifedipine, an L-type Ca 2+ channel blocker (Woo et al, 2013), but no inhibitory effect of nifedipine was observed in p38 phosphorylation, suggesting that Ca 2+ influx through L-type Ca 2+ channels is required for the selective activation of ERK and seems to operate independently of p38 signaling (Mulvaney, Zhang, Fewtrell, & Roberson, 1999;Tada et al, 2010). In addition to L-type Ca 2+ channels, CaSRs have also been confirmed to mediate MTA-induced biological reactions in several recent studies (J. M. Kim et al, 2017;Mizumachi et al, 2017;Yasukawa et al, 2017). Additionally, a mixture of MTA with 5% CaCl 2 and 2.5% Na 2 HPO 4 promoted better differentiation in human DPCs than conventional MTA alone via the upregulation of DSPP and COL1 gene expression (Kulan, Karabiyik, Kose, & Kargul, 2017), supporting the concept that extracellular Ca 2+ and P ions could combinatorially affect osteo/odontoblastic differentiation induced by MTA through the targeting of osteoblast marker expression.…”

Section: Osteo/odontogenic Differentiationmentioning

confidence: 99%

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The emerging role of extracellular Ca²⁺ in osteo/odontogenic differentiation and the involvement of intracellular Ca²⁺ signaling: From osteoblastic cells to dental pulp cells and odontoblasts

2018

Journal Cellular Physiology

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Calcium ions (Ca ) is the main element of dental pulp capping materials. Ca signaling plays a crucial role in a myriad of cell activities. An overwhelming array of studies have already reported the experimental and clinical benefits of Ca -enriched materials in the treatment of teeth with accidental vital pulp exposure and incomplete root formation. Thus, Ca signaling has always been an excellent target for the design of various novel biomaterials for use in revitalizing or regenerative endodontic procedures. However, the molecular mechanisms that enable dental pulp cells (DPCs) to detect and respond to extracellular Ca have not been characterized in detail before. In this review, we mainly outline the pathways by which the cell detects and responds to extracellular Ca , as well as the relevant regulatory paths in DPCs and odontoblasts, and discuss the potential role of Ca as a therapeutic tool. Moreover, because DPCs share many of the same functional properties that are found in osteoblasts, some comparisons with bone cells were additionally incorporated into this text.

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“…Dental caries and pulpitis are the most common oral disorders caused by bacterial penetration and subsequent inflammation of pulp tissues that can alter the differentiation of dental pulp cells . During bacterial infection or trauma, dental pulp odontoblasts proliferate and differentiate to form a reparative dentine that prevents lesions . AS‐IV has been reported to affect RANKL‐induced osteoclastogenesis, and RANKL signaling is related to odontoblastic differentiation .…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV attenuates inflammatory injury and promotes odontoblastic differentiation in lipopolysaccharide‐stimulated MDPC‐23 cells and rat pulpitis

Ding¹,

Gao

Zheng³

et al. 2019

J Oral Pathology Medicine

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Background Astragaloside IV (AS‐IV), a natural herbal compound from Astragalus membranaceus, has inhibitory effects on receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis, and RANKL signal helps to regulate odontoblast differentiation. However, whether and how AS‐IV affects odontoblastic differentiation remains unclear. Methods Lipopolysaccharide (LPS)‐stimulated MDPC‐23 cells and rat pulpitis were treated with AS‐IV, cell viability, and LDH leakage was analyzed by CCK‐8 assay and LDH Leakage assay. The production of TNF‐α and IL‐6 was determined by ELISA and qRT‐PCR assay. The expression of alkaline phosphatase (ALP) was detected using an ALP assay kit, and the expression of dentin sialophos‐phoprotein (DSPP), dentin matrix protein‐1 (DMP1), basic fibroblast growth factor (FGF2), and phosphorylated extracellular signal‐regulated kinase (p‐ERK) was determined by western blot. Results AS‐IV dose dependently increased in cell viability and decreased the overproduction of TNF‐α and IL‐6 in LPS‐stimulated MDPC‐23 cells. AS‐IV also counteracted LPS‐induced downregulation of ALP, DSPP, and DMP1 in MDPC‐23 cells. Furthermore, AS‐IV significantly decreased the expression of FGF2 and p‐ERK in LPS‐stimulated MDPC‐23 cells. More important, the addition of FGF2 partly neutralized AS‐IV‐mediated inhibition of FGF2/ERK signaling, abolished AS‐IV‐induced reduction of TNF‐α and IL‐6, and counteracted AS‐IV‐induced upregulation of DSPP and DMP‐1 in these cells. Meanwhile, AS‐IV inhibited the excessive production of TNF‐α and IL‐6, suppressed the downregulation of DSPP and DMP1, and disturbed the up‐regulation of FGF2 and p‐ERK in the pulp tissues of rat pulpitis model. Conclusions AS‐IV exerted anti‐inflammatory and pro‐differentiation effects in LPS‐stimulated MDPC‐23 cells and rat pulpitis via inhibiting the FGF2/ERK signaling pathway.

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Calcium-sensing receptor-ERK signaling promotes odontoblastic differentiation of human dental pulp cells

Cited by 40 publications

References 38 publications

Senescence and odontoblastic differentiation of dental pulp cells

Senescence and odontoblastic differentiation of dental pulp cells

The emerging role of extracellular Ca²⁺ in osteo/odontogenic differentiation and the involvement of intracellular Ca²⁺ signaling: From osteoblastic cells to dental pulp cells and odontoblasts

Astragaloside IV attenuates inflammatory injury and promotes odontoblastic differentiation in lipopolysaccharide‐stimulated MDPC‐23 cells and rat pulpitis

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Calcium-sensing receptor-ERK signaling promotes odontoblastic differentiation of human dental pulp cells

Cited by 40 publications

References 38 publications

Senescence and odontoblastic differentiation of dental pulp cells

Senescence and odontoblastic differentiation of dental pulp cells

The emerging role of extracellular Ca2+ in osteo/odontogenic differentiation and the involvement of intracellular Ca2+ signaling: From osteoblastic cells to dental pulp cells and odontoblasts

Astragaloside IV attenuates inflammatory injury and promotes odontoblastic differentiation in lipopolysaccharide‐stimulated MDPC‐23 cells and rat pulpitis

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The emerging role of extracellular Ca²⁺ in osteo/odontogenic differentiation and the involvement of intracellular Ca²⁺ signaling: From osteoblastic cells to dental pulp cells and odontoblasts