Chitooligosaccharide inhibits RANKL‐induced osteoclastogenesis and ligation‐induced periodontitis by suppressing MAPK/ c‐fos/NFATC1 signaling

Xu, Weifeng; Chen, Xinwei; Fan, Baoting; Guo, Ke; Chen, Yang; Yu, Shiqi; Pang, Yichuan; Zhang, Sam

doi:10.1002/jcp.29207

Cited by 21 publications

(18 citation statements)

References 33 publications

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“…ROBO1 receptor was upregulated in PAPT of Slit2 -Tg mice compared to wild type mice. MAPK signaling is a key regulator of inflammation and osteoclastogenesis ( Li et al, 2012 ; Xu et al, 2020 ). Expression of MAPK signaling related factors MAPK14 and p-p38 was upregulated in the PAPT of Slit2 -Tg mice.…”

Section: Discussionmentioning

confidence: 99%

“…Activated inflammatory cascade elevates the level of pro-inflammatory cytokines in periodontal tissue, including IL-6, IL-1β, and TNF-α. Elevated levels of pro-inflammatory cytokines in alveolar bone induce osteoclastogenesis and osteoclastogenic bone resorption ( Pan et al, 2019 ; AlQranei and Chellaiah, 2020 ; Xu et al, 2020 ). Activation of MAPK (p38) signaling in various immune cells regulates periodontal disease progression and alveolar bone loss ( Li et al, 2012 ; Xu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Elevated levels of pro-inflammatory cytokines in alveolar bone induce osteoclastogenesis and osteoclastogenic bone resorption ( Pan et al, 2019 ; AlQranei and Chellaiah, 2020 ; Xu et al, 2020 ). Activation of MAPK (p38) signaling in various immune cells regulates periodontal disease progression and alveolar bone loss ( Li et al, 2012 ; Xu et al, 2020 ). SLIT2 contributes to cholestatic fibrosis via activation of MAPK p38 signaling in hepatic stellate cells ( Li et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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SLIT2 Overexpression in Periodontitis Intensifies Inflammation and Alveolar Bone Loss, Possibly via the Activation of MAPK Pathway

Wang

Zheng

Pathak

et al. 2020

Front. Cell Dev. Biol.

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SLIT2, a member of neuronal guidance cues, has been reported to regulate inflammation and cancer progression. Periodontitis is an oral inflammatory disease that degenerates periodontal tissue, alveolar bone and tooth. This study aims to explore the expression pattern of SLIT2 in periodontitis and its role in disease progression and bone loss. Gingival tissue of 20 periodontitis patients and 20 healthy-controls was obtained. Ligature-induced periodontitis (LIP) mice-model was developed in Slit2-Tg and wild-type mice. The effect of SLIT2 on inflammation, immune cell infiltration, M1 macrophage polarization, and alveolar bone loss in periodontitis was analyzed extensively. In periodontitis-affected gingival-tissue, SLIT2 expression was 4.4-fold higher compared to healthy-volunteers. LIP enhanced SLIT2 expression in mice periodontitis-affected periodontal tissue (PAPT) and blood circulation of wild-type mice by 4. 6-, and 5.0-fold, respectively. In Slit2-Tg-mice PAPT, SLIT2 expression was 1.8-fold higher compared to wild-type mice. Micro-CT and histomorphometric analysis revealed a 1.3-fold higher cement-enamel-junction to the alveolar-bone-crest (CEJ-ABC) distance and alveolar bone loss in LIP Slit2-Tg-mice compare to LIP wild-type mice. Results from RNA-sequencing, RT-qPCR, and ELISA showed a higher expression of Cxcr2, Il-18, TNFα, IL-6, and IL-1β in Slit2-Tg-mice PAPT compared to wild-type-mice. Slit2-Tg-mice PAPT showed a higher number of osteoclasts, M1 macrophages, and the upregulation of Robo1 expression. Slit2-Tg-mice PAPT showed upregulation of M1 macrophage marker CD16/32 and osteoclastogenic markers Acp5 , Ctsk , and Nfatc1 , but osteogenic markers ( Alp, Bglap ) remained unchanged. Immunohistochemistry unveiled the higher vasculature and infiltration of leucocytes and macrophages in Slit2-Tg-mice PAPT. RNA-sequencing, GO-pathway enrichment analysis, and western blot analysis revealed the activation of the MAPK signaling pathway in Slit2 -Tg mice PAPT. In conclusion, SLIT2 overexpression in periodontitis intensifies inflammation, immune cells infiltration, M1 macrophage polarization, osteoclastogenesis, and alveolar bone loss, possibly via activation of MAPK signaling, suggesting the role of SLIT2 on exacerbation of periodontitis and alveolar bone loss.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SLIT2 Overexpression in Periodontitis Intensifies Inflammation and Alveolar Bone Loss, Possibly via the Activation of MAPK Pathway

Wang

Zheng

Pathak

et al. 2020

Front. Cell Dev. Biol.

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“…The genes we chose in this study were derived from differentially expressed genes that also had an interaction network with several key genes, including INS (insulin), SST (somatostatin), and GCG (glucagon). FOS and RPS6KA6 are members of the MAPK signaling pathway, which is a vital pathway for cell differentiation and proliferation [29,30]. Tuning these genes may contribute to the transdifferentiation of cBMSCs into IPCs.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Analysis Reveals Changes in Long Noncoding RNAs in the Differentiation of Canine BMSCs into Insulin-Producing Cells

Wang

Dai

Gao

et al. 2020

IJMS

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Long noncoding RNAs (lncRNAs) have been extensively explored over the past decade, including mice and humans. However, their impact on the transdifferentiation of canine bone marrow mesenchymal stem cells (cBMSCs) into insulin-producing cells (IPCs) is largely unknown. In this study, we used a three-step induction procedure to induce cBMSCs into IPCs, and samples (two biological replicates each) were obtained after each step; the samples consisted of “BMSCs” (B), “stage 1” (S1), “stage 2” (S2), “stage 3” (S3), and “islets” (I). After sequencing, 15,091 lncRNAs were identified, and we screened 110, 41, 23, and 686 differentially expressed lncRNAs (padjusted < 0.05) in B vs. S1, S1 vs. S2, S2 vs. S3, and I vs. S3 pairwise comparisons, respectively. In lncRNA target prediction, there were 166,623 colocalized targets and 2,976,362 correlated targets. Gene Ontology (GO) analysis showed that binding represented the main molecular functions of both the cis- and trans-modes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that the insulin signaling pathway, Rap1 signaling pathway, tight junctions, MAPK signaling pathway, and cell cycle were enriched for these relative genes. The expression of lncRNAs was verified using qRT-PCR. This study provides a lncRNA catalog for future research concerning the mechanism of the transdifferentiation of cBMSCs into IPCs.

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“…One such signaling pathway is mediated through calcium efflux inside the cells leading to activation of a key transcription factor called as nuclear factor of activated T cells 1 (NFATc1) (Yang et al, 2018). The regulation of NFATc1 is controlled by kinases (PI3K/Akt and mitogen‐activated protein kinases [MAPKs]), transcription factors (NFκB and STAT3) and secondary messengers inside the cells (Cheon et al, 2016; Jia et al, 2019; Nakanishi & Tsukamoto, 2015; Xu et al, 2019). Continuous sequestration of NFATc1 inside mature osteoclasts leads to the release of acidic enzymes in the synovium such as tartarate acid phosphatase (TRAP), matrix metalloproteinases (MMPs), carbonic anhydrase II and Cathepsin K that degrade the bone and matrix (Chaweewannakorn et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

miR‐506‐3p alleviates uncontrolled osteoclastogenesis via repression of RANKL/NFATc1 signaling pathway

Dinesh

Kalaiselvan

Sujitha

et al. 2020

Journal Cellular Physiology

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Bone erosion is the major cause of deformities in autoimmune disease conditions such as osteoporosis and rheumatoid arthritis. Aberrant receptor activator of nuclear factor kappa B ligand (RANKL) secretion in bone disorders have been implicated to promote uncontrolled osteoclast differentiation through the regulation of nuclear factor of activated T cells 1 (NFATc1) transcription factor. This phenomenon is governed by several molecular factors including microRNAs, which are under‐expressed during disease progression. This report focuses on elucidating the molecular mechanism of miR‐506‐3p towards the RANKL/NFATc1 pathway. miR‐506‐3p showed high binding affinity towards NFATc1 (ΔG = −22.4 kcal/mol). Bone marrow‐derived macrophages (BMMs) isolated from rats stimulated with RANKL (100 ng/ml) showed active expression of NFATc1 which differentiated into mature osteoclasts. Moreover, NFATc1 activation resulted in downstream secretion of various bone resorptive enzymes (cathepsin K, carbonic anhydrase II, tartarate acid phosphatase, and matrix metalloproteinase 9) which lead to active bone resorption. However, transfection of miR‐506‐3p resulted in selective repression of NFATc1 inside the cells. This further resulted in the diminished release of bone resorptive enzymes that were essential for the degradation of the bone. Overall, we predict that miR‐506‐3p can be used as a molecular intervention for RANKL/NFATc1 mediated osteoclastogenesis.

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Chitooligosaccharide inhibits RANKL‐induced osteoclastogenesis and ligation‐induced periodontitis by suppressing MAPK/ c‐fos/NFATC1 signaling

Cited by 21 publications

References 33 publications

SLIT2 Overexpression in Periodontitis Intensifies Inflammation and Alveolar Bone Loss, Possibly via the Activation of MAPK Pathway

SLIT2 Overexpression in Periodontitis Intensifies Inflammation and Alveolar Bone Loss, Possibly via the Activation of MAPK Pathway

Genome-Wide Analysis Reveals Changes in Long Noncoding RNAs in the Differentiation of Canine BMSCs into Insulin-Producing Cells

miR‐506‐3p alleviates uncontrolled osteoclastogenesis via repression of RANKL/NFATc1 signaling pathway

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