Roles of SP600125 in expression of JNK, RANKL and OPG in cultured dental follicle cells

Wang, Qi; Yuan, Xiaocong; Li, Boqi; Sun, Dawei; Liu, Jia; Liu, Tao; Bi, Xiaojuan

doi:10.1007/s11033-019-04745-3

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…In humans, MSX1 is also restricted to the dental mesenchyme as in mice ( Lin et al, 2007 ) and is a crucial player in human odontogenesis as evidenced by the fact that mutation in MSX1 results in Rieger syndrome, which exhibits severe tooth agenesis. To determine whether the regulation of MSX1 expression by BMP/pSMAD1/5/8 is conserved during early human tooth development, we performed a small-molecule inhibition experiment using dorsomorphin (SMAD1/5/8 phosphorylation inhibitor) to specifically block transduction of BMP/pSMAD1/5/8 signaling pathway and combination of SB203508 (p38 MAPK inhibitor), U0126 (ERK1/2 inhibitor), and SP600125(JNK inhibitor) to specifically block BMP/MAPK signaling pathway ( Xiao et al, 2017 ; Liu et al, 2018 ; Wang et al, 2019 ) in cap-stage human molar germs cultured in vitro with the Trowell-type organ culture system. Immunostaining showed that, after cultured for 24 h, the expression of MSX1 was dramatically downregulated in dorsomorphin-treated molar tooth germs ( Figure 2B ), whereas it was hardly disturbed when treated with the combination of SB203508, U0126, and SP600125 ( Figure 2C ) as compared with that treated with DMSO ( Figure 2A ).…”

Section: Resultsmentioning

confidence: 99%

Operation of the Atypical Canonical Bone Morphogenetic Protein Signaling Pathway During Early Human Odontogenesis

Lin

Ruan

et al. 2022

Front. Physiol.

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Bone morphogenetic protein (BMP) signaling plays essential roles in the regulation of early tooth development. It is well acknowledged that extracellular BMP ligands bind to the type I and type II transmembrane serine/threonine kinase receptor complexes to trigger the BMP signaling pathway. Then, the receptor-activated Smad1/5/8 in cytoplasm binds to Smad4, the central mediator of the canonical BMP signaling pathway, to form transfer complexes for entering the nucleus and regulating target gene expression. However, a recent study revealed the functional operation of a novel BMP-mediated signaling pathway named the atypical BMP canonical signaling pathway in mouse developing tooth, which is Smad1/5/8 dependent but Smad4 independent. In this study, we investigated whether this atypical BMP canonical signaling is conserved in human odontogenesis. We showed that pSMAD1/5/8 is required for the expression of Msh homeobox 1 (MSX1), a well-defined BMP signaling target gene, in human dental mesenchyme, but the typical BMP canonical signaling is in fact not operating in the early human developing tooth, as evidenced by the absence of pSMAD1/5/8-SMAD4 complexes in the dental mesenchyme and translocation of pSMAD1/5/8, and the expression of MSX1 induced by BMP4 is mothers against decapentaplegic homolog 4 (SMAD4)-independent in human dental mesenchymal cells. Moreover, integrative analysis of RNA-Seq data sets comparing the transcriptome profiles of human dental mesenchymal cells with and without SMAD4 knockdown by siRNA displays unchanged expression profiles of pSMAD1/5/8 downstream target genes, further affirming the functional operation of the atypical canonical BMP signaling pathway in a SMAD1/5/8-dependent but SMAD4-independent manner in the dental mesenchyme during early odontogenesis in humans.

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Section: Resultsmentioning

confidence: 99%

Operation of the Atypical Canonical Bone Morphogenetic Protein Signaling Pathway During Early Human Odontogenesis

Lin

Ruan

et al. 2022

Front. Physiol.

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“…However, the regulatory mechanisms of dental follicles in tooth eruption are still unclear 34,35 . RANKL can be secreted by osteocytes 36,37 and dental follicle cells 38,39 . To elaborate the mechanisms by which RANKL expression in the coronal dental follicle is increased by isorhamnetin 3-O-neohesperid, RANKL-related signalling pathways and transcriptional factors in dental follicle cells and osteocytes are worthy of further study in future.…”

Section: Discussionmentioning

confidence: 99%

Isorhamnetin 3-O-neohesperidoside promotes the resorption of crown-covered bone during tooth eruption by osteoclastogenesis

Zheng

Shang

et al. 2020

Sci Rep

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Delayed resorption of crown-covered bone is a critical cause of delayed tooth eruption. Traditional herbal medicines may be good auxiliary treatments to promote the resorption of crown-covered bone. This study was carried out to analyse the effect of isorhamnetin 3-O-neohesperidoside on receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclastogenesis in vitro and resorption of the crown-covered bone of the lower first molars in mice in vivo. Isorhamnetin 3-O-neohesperidoside promoted osteoclastogenesis and the bone resorption of mouse bone marrow macrophages (BMMs) and upregulated mRNA expression of the osteoclast-specific genes cathepsin K (CTSK), vacuolartype H +-ATPase d2(V-ATPase d2), tartrate resistant acid phosphatase (TRAP) and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). NFATc1, p38 and AKT signalling was obviously activated by isorhamnetin 3-O-neohesperidoside in osteoclastogenesis. Isorhamnetin 3-O-neohesperidoside aggravated resorption of crown-covered bone in vivo. In brief, isorhamnetin 3-O-neohesperidoside might be a candidate adjuvant therapy for delayed intraosseous eruption. The development of osseous eruption is an indispensable stage in the tooth eruption process 1,2. Osteoclast differentiation is stimulated, causing the resorption of crown-covered bone of an erupting tooth, which forms an intraosseous eruption canal 3. Osteoclastogenesis in the crown-covered bone is essential. Impaired osseous eruption, in which osteoclastogenesis is disturbed, is common in clinical practice 4 and can manifest as either delayed or the complete absence of eruption 5,6. Although unerupted teeth are usually asymptomatic, they may cause cosmetic and pathologic complications 4 Treatments include orthodontic uprighting, surgical-orthodontic uprighting, surgical uprighting, surgical repositioning, surgical exposure or the removal of pathologic conditions 7. However, these treatments are very complex and invasive. Research shows that osteoclastogenesis is regulated by a key factor termed receptor activator of NF-κB ligand (RANKL). RANKL agonists or osteoclastogenesis-related drugs can be used to treat delayed tooth eruption 8,9. Traditional Chinese medicine, which is without toxic side effects may also be a good auxiliary treatment for delayed tooth eruption. Isorhamnetin 3-O-neohesperidin, known as Pu huang in Chinese 10 , is the main active substance of T. angustifolia, can also be isolated from the leaves of Acacia salicina 11. Because of its antioxidant, antiatherogenic and anti-inflammatory activities, Pu Huang has been widely used for the treatment of haematuria, dysmenorrhea, uterine bleeding and trauma in China for a long time 12. Isorhamnetin 3-O-neohesperidin has been reported to protect cells against oxidative stress by inhibiting H 2 O 2-induced genotoxicity and DNA damage induced by hydroxyl radicals 13. Intestinal flora including Escherichia sp. 23 and sp. 30, can convert isorhamnetin 3-O-neohesperidin to three main metabolites, isorhamnetin-3-O-glucoside(I3OG), isorhamnet...

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“…The expression of RANKL was increased while OPG was inhibited during tooth eruption [10] . Wnt(Wingless and INT -1)/β-catenin, RUNX2(runt-related transcription factor 2)-MiR31-SATB2(sensor array test-bed 2), JNK (Jun N-terminal kinase) and other signaling pathways are involved in alveolar bone resorption [11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

The expressions of tooth eruption relevant genes are different in incisors and molars dental follicle cells in rat: an in vitro study

Dong

Wang

et al. 2019

Preprint

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Background The incisors and molars showed different patterns of tooth eruption in rodents and the dental follicle cells play key roles in tooth eruption. Little is known about the differences in incisors and molars dental follicle cells during tooth eruption in rodents. The purpose of this study was to investigate the differences between incisor dental follicle cells and molar dental follicle cells during tooth eruption in rat.Methods Incisor dental follicle cells and molar dental follicle cells were obtained as previously described. Immunofluorescence was used to identify the cells. Gene expression was measured by real-time qPCR and western blot.Results Compared with molar dental follicle cells, the incisor dental follicle cells showed higher expression of OPG, BMP-2 and BMP-3. The molar dental follicle cells showed higher expression of MCP-1 and RANKL.Conclusions The expression patterns of genes related to tooth eruption were different in incisors and molars dental follicle cells in rat.

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Roles of SP600125 in expression of JNK, RANKL and OPG in cultured dental follicle cells

Cited by 5 publications

References 30 publications

Operation of the Atypical Canonical Bone Morphogenetic Protein Signaling Pathway During Early Human Odontogenesis

Operation of the Atypical Canonical Bone Morphogenetic Protein Signaling Pathway During Early Human Odontogenesis

Isorhamnetin 3-O-neohesperidoside promotes the resorption of crown-covered bone during tooth eruption by osteoclastogenesis

The expressions of tooth eruption relevant genes are different in incisors and molars dental follicle cells in rat: an in vitro study

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