Baicalin Promotes Osteogenic Differentiation of Human Cementoblast Lineage Cells Via the Wnt/β Catenin Signaling Pathway

Kimura, Aya Hirata; Kunimatsu, Ryo; Yoshimi, Yuki; Tsuka, Yuji; Awada, Tetsuya; Horie, Kayo; Gunji, Hidemi; Abe, Takaharu; Nakajima, Kengo; Kitagawa, Masae; Miyauchi, Mutsumi; Takata, Takashi; Tanimoto, Kotaro

doi:10.2174/1381612824666181116103514

Cited by 9 publications

(15 citation statements)

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“…In our experiment we demonstrated that the expression of Runx-2, an essential transcription factor for osteoblast differentiation, mineralization and migration (Bosshardt, 2005;Liu and Lee, 2013) as well as for cementogenesis (Hakki et al, 2018) was strongly up-regulated in OCCM-30 cells in response to high concentrations of Adiponectin. Adiponectin-induced Runx-2 upregulation in cementoblasts may be interpreted in the circumstances of wound healing and cementum repair and regeneration, because the regulatory role that Runx-2 exerts in cementum formation (Kimura et al, 2018). F-Spondin, a cementoblast specific gene that orchestrate cementoblast differentiation (Kitagawa et al, 2012), was also up-regulated by Adiponectin.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin Interacts In-Vitro With Cementoblasts Influencing Cell Migration, Proliferation and Cementogenesis Partly Through the MAPK Signaling Pathway

et al. 2020

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Current clinical evidences suggest that circulating Adipokines such as Adiponectin can influence the ratio of orthodontic tooth movement. We aimed to investigate the effect that Adiponectin has on cementoblasts (OCCM-30) and on the intracellular signaling molecules of Mitogen-activated protein kinase (MAPK). We demonstrated that OCCM-30 cells express AdipoR1 and AdipoR2. Alizarin Red S staining revealed that Adiponectin increases mineralized nodule formation and quantitative AP activity in a dose-dependent manner. Adiponectin up-regulates the mRNA levels of AP, BSP, OCN, OPG, Runx-2 as well as F-Spondin. Adiponectin also increases the migration and proliferation of OCCM-30 cells. Moreover, Adiponectin induces a transient activation of JNK, P38, ERK1/2 and promotes the phosphorylation of STAT1 and STAT3. The activation of Adiponectin-mediated migration and proliferation was attenuated after pharmacological inhibition of P38, ERK1/2 and JNK in different degrees, whereas mineralization was facilitated by MAPK inhibition in varying degrees. Based on our results, Adiponectin favorably affect OCCM-30 cell migration, proliferation as well as cementogenesis. One of the underlying mechanisms is the activation of MAPK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Adiponectin Interacts In-Vitro With Cementoblasts Influencing Cell Migration, Proliferation and Cementogenesis Partly Through the MAPK Signaling Pathway

et al. 2020

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“…In recent years, the role of canonical Wnt signaling in cementum formation and regeneration has been extensively studied with controversial and inconsistent results. [26][27][28][29][30][31][32][33][34][35] Here, we analyzed the effect of constitutively active canonical Wnt signaling during cementum formation in vivo using transgenic mice with constitutively activated β-catenin in Dmp1-lineage cells (fl/+). In vitro validation was performed under different levels of Wnt activation to better understand the intracellular signal transduction of cementocytes and molecular mechanisms controlling cementogenesis and mineralization.…”

Section: Discussionmentioning

confidence: 99%

“…25 Current data from investigating the role of canonical Wnt signaling in cementum formation, however, are controversial and inconsistent between studies. [26][27][28][29][30][31][32][33][34][35] An experimental study shows that both gene levels of cementum protein1 (CEMP1) and cementum attached protein (CAP), the markers of cementogenic differentiation, are elevated in periodontal ligament cells (PDLCs) via Wnt/β-catenin signaling pathway under hypoxia conditions. 26 Accordingly, incorporation of Li(+) ions into bioactive materials has been reported as a viable means of enhancing the Wnt canonical signaling pathway to stimulate proliferation and cementogenic differentiation of PDLCs in several periodontal tissue engineering applications.…”

Section: Introductionmentioning

confidence: 99%

“…27,28 The Wnt/βcatenin signaling pathway has also been found to enhance osteogenic differentiation of human cementoblast cells and promote differentiation of human bone marrowderived mesenchymal stem cells into cementoblast-like cells in vitro. 29,30 Wnt-responsive stem or progenitor cells originating in the periodontal ligament were closely related to the physiological cementum repair. 11 Even so, increasing evidence has provided the opposite conclusion that cementum formation could be inhibited when the Wnt/β-catenin pathway is activated or potentially overactivated.…”

Section: Introductionmentioning

confidence: 99%

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Canonical Wnt/β‐catenin signaling has positive effects on osteogenesis, but can have negative effects on cementogenesis

Wang

Jiang

et al. 2022

Journal of Periodontology

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Background To date, therapeutic approaches for cementum regeneration are limited and outcomes remain unpredictable. A significant barrier to improve therapies for cementum regeneration is that the cementocyte and its intracellular signal transduction mechanisms remain poorly understood. This study aims to elucidate the regulatory mechanism of Wnt pathway in cementogenesis. Methods The effects of canonical Wnt signaling were compared in vitro using immortalized murine cementocyte cell line IDG‐CM6 and osteocyte cell line IDG‐SW3 by quantitative real‐time polymerase chain reaction, Western blot, confocal microscopy, alkaline phosphatase (ALP) assay, and Alizarin red S staining. In vivo, histological changes of cementum and bone formation were examined in transgenic mice in which constitutive activation of β‐catenin is driven by Dmp1 promoter. Results Expression of components of the Wnt/β‐catenin pathway were much greater in the IDG‐SW3 cells compared with the IDG‐CM6 cells resulting in much lower expression of Sost/sclerostin in the IDG‐SW3 cells. In the IDG‐CM6 cells, low dose Wnt3a (20 ng/ml) had a modest effect while high dose (200 ng/ml) inhibited runt‐related transcription factor 2, osterix, ALP, and osteopontin in contrast to the IDG‐SW3 cells where high dose Wnt3a dramatically increased mRNA expression of these same markers. However, high Wnt3a significantly increased mRNA for components of Wnt/β‐catenin signaling pathway in both IDG‐CM6 and IDG‐SW3 cells. In vivo, constitutive activation of β‐catenin in the Dmp1‐lineage cells in mice leads to bone hyperplasia and cementum hypoplasia. Conclusion These findings indicate that Wnt signaling has distinct and different effects on the regulation of long bone as compared with cementum.

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“…We previously reported that baicalin enhances the osteogenic differentiation of human cementoblast-lineage cells through the Wnt/beta (Wnt/β)-catenin signaling pathway in vitro . 18 Furthermore, baicalin ingestion during experimental tooth movement in rats increases osteoprotegerin (OPG), decreases the expression of receptor activator of nuclear factor-kB ligand (RANKL), and suppresses root resorption. 19 Consequently, it is assumed that baicalin may affect metabolic regulation by bone resorption markers in human cementoblast-lineage cells.…”

Section: Introductionmentioning

confidence: 99%

Effects of baicalin on the proliferation and expression of OPG and RANKL in human cementoblast-lineage cells

Kunimatsu¹,

Kimura²,

Sakata³

et al. 2022

Journal of Dental Sciences

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Background/purpose Baicalin, a natural bioactive flavonoid extracted from Scutellaria baicalensis Georgi, mediates bone metabolism, and recent studies have revealed that it has cell signaling properties. However, its biological functions in cementoblasts still remain unclear. This study therefore aimed to investigate the effects of baicalin on bone resorption markers, including osteoprotegerin (OPG) and receptor activator of nuclear factor-κβ ligand (RANKL), in human cementoblast-lineage cells, as well as their proliferation ability. Materials and methods Human cementoblast cell line (HCEM) cells were cultured and treated with 0, 0.01, 0.1, or 1 μM of baicalin. The proliferative capacity of cultured HCEM cells was analyzed using bromodeoxyuridine immunoassay and cell counting. The baicalin effect on OPG and RANKL expression was determined using quantitative polymerase chain reaction (qPCR) and western blotting. Furthermore, OPG expression was measured in 1 μM baicalin-treated HCEM cells in the presence or absence of the Wnt signaling pathway inhibitor, Dickkopf (Dkk)-1, using qPCR and western blotting. Results The addition of 0.01, 0.1, and 1 μM of baicalin did not significantly change the proliferative capacity of cultured HCEM cells. Compared with the non-supplemented group, baicalin increased and suppressed OPG and RANKL gene and protein expression, respectively, in a concentration-dependent manner. OPG mRNA and protein expression levels were increased by 1 μM baicalin, which was suppressed by Dkk-1 addition. Conclusion Baicalin enhanced OPG expression in HCEM cells through the Wnt/beta-catenin signaling pathway, which could contribute to periodontal tissue regeneration.

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Baicalin Promotes Osteogenic Differentiation of Human Cementoblast Lineage Cells Via the Wnt/β Catenin Signaling Pathway

Cited by 9 publications

References 0 publications

Adiponectin Interacts In-Vitro With Cementoblasts Influencing Cell Migration, Proliferation and Cementogenesis Partly Through the MAPK Signaling Pathway

Adiponectin Interacts In-Vitro With Cementoblasts Influencing Cell Migration, Proliferation and Cementogenesis Partly Through the MAPK Signaling Pathway

Canonical Wnt/β‐catenin signaling has positive effects on osteogenesis, but can have negative effects on cementogenesis

Effects of baicalin on the proliferation and expression of OPG and RANKL in human cementoblast-lineage cells

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