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BMC Oral Health
Published in: BMC Oral Health 1/2023

Open Access 01-12-2023 | Research

Oridonin alleviates the inhibitory effect of lipopolysaccharide on the proliferation and osteogenic potential of periodontal ligament stem cells by inhibiting endoplasmic reticulum stress and NF-κB/NLRP3 inflammasome signaling

Authors: Junhao Jiang, Nong Zhang, Haibo Song, Ya Yang, Juan Li, Xiaoli Hu

Published in: BMC Oral Health | Issue 1/2023

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Abstract

Background

The aim of this study was to investigate the protective effect and mechanism of oridonin in an in vitro lipopolysaccharide (LPS)-induced human periodontal ligament stem cells (hPDLSCs) model of periodontitis.

Methods

Primary hPDLSCs were isolated and cultured, and then the expression of surface antigens CD146, STRO-1 and CD45 of hPDLSCs was detected by flow cytometry. The mRNA expression level of Runx2, OPN, Col-1, GRP78, CHOP, ATF4 and ATF6 in the cells was tested by qRT-PCR. MTT was taken to determine the cytotoxicity of oridonin at different concentrations (0–4 μM) on hPDLSCs. Besides, ALP staining, alizarin red staining and Oil Red O staining were utilized to assess the osteogenic differentiation (ALP concentration, mineralized calcium nodule formation) and adipogenic differentiation abilities of the cells. The proinflammatory factors level in the cells was measured by ELISA. The protein expression level of NF-κB/NLRP3 pathway-related proteins and endoplasmic reticulum (ER) stress-related markers in the cells were detected by Western blot.

Results

hPDLSCs with positive CD146 and STRO-1 expression and negative CD45 expression were successfully isolated in this study. 0.1–2 μM of oridonin had no significant cytotoxicity on the growth of hPDLSCs, while 2 μM of oridonin could not only greatly reduce the inhibitory effect of LPS on the proliferation and osteogenic differentiation of hPDLSCs cells, but also inhibit LPS-induced inflammation and ER stress in hPDLSCs cells. Moreover, further mechanism research showed that 2 μM of oridonin suppressed NF-κB/NLRP3 signaling pathway activity in LPS-induced hPDLSCs cells.

Conclusions

Oridonin promotes proliferation and osteogenic differentiation of LPS-induced hPDLSCs in an inflammatory environment, possibly by inhibiting ER stress and NF-κB/NLRP3 pathway. Oridonin may have a potential role in the repair and regeneration of hPDLSCs.
Appendix
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Literature
1.
Serrano C, Suarez E. Prevalence of severe periodontitis in a colombian adult population. J Int Acad Periodontol. 2019;21:53–62.PubMed
2.
Bosshardt DD, Stadlinger B, Terheyden H. Cell-to-cell communication–periodontal regeneration. Clin Oral Implants Res. 2015;26:229–39.CrossRefPubMed
3.
Xu XY, Li X, Wang J, He XT, Sun HH, Chen FM. Concise review: periodontal tissue regeneration using stem cells: strategies and translational considerations. Stem Cells Transl Med. 2019;8:392–403.CrossRefPubMed
4.
Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet. 2004;364:149–55.CrossRefPubMed
5.
Zhang Y, Xing Y, Jia L, Ji Y, Zhao B, Wen Y, et al. An in vitro comparative study of multisource derived human mesenchymal stem cells for bone tissue engineering. Stem Cells Dev. 2018;27:1634–45.CrossRefPubMed
6.
7.
Tan J, Zhou L, Xue P, et al. Tumor necrosis factor-α attenuates the osteogenic differentiation capacity of periodontal ligament stem cells by activating PERK signaling. J Periodontol. 2016;87:e159–71.CrossRefPubMed
8.
Huck O, Elkaim R, Davideau JL, Tenenbaum H. Porphyromonas gingivalis-impaired innate immune response via NLRP3 proteolysis in endothelial cells. Innate Immun. 2015;21:65–72.CrossRefPubMed
9.
Pizzicannella J, Fonticoli L, Guarnieri S, Marconi GD, Rajan TS, Trubiani O, Diomede F. Antioxidant ascorbic acid modulates NLRP3 inflammasome in LPS-G treated oral stem cells through NF-κB/caspase-1/IL-1β Pathway. Antioxidants (Basel). 2021;10(5):797.CrossRefPubMed
10.
SoundaraRajan T, Giacoppo S, Diomede F, Bramanti P, Trubiani O, Mazzon E. Human periodontal ligament stem cells secretome from multiple sclerosis patients suppresses NALP3 inflammasome activation in experimental autoimmune encephalomyelitis. Int J Immunopathol Pharmacol. 2017;30(3):238–52.CrossRef
11.
12.
13.
Liu W, Huang G, Yang Y, Gao R, Zhang S, Kou B. Oridonin inhibits epithelial-mesenchymal transition of human nasopharyngeal carcinoma cells by negatively regulating AKT/STAT3 signaling pathway. Int J Med Sci. 2021;18:81–7.CrossRefPubMedPubMedCentral
14.
Hu X, Wang Y, Gao X, Xu S, Zang L, Xiao Y, et al. Recent progress of oridonin and its derivatives for the treatment of acute myelogenous leukemia. Mini Rev Med Chem. 2020;20:483–97.CrossRefPubMed
15.
Zhang T, Chen Y, Zhan Z, Mao Z, Wen Y, Liu S, et al. Oridonin alleviates d-GalN/LPS-induced acute liver injury by inhibiting NLRP3 inflammasome. Drug Dev Res. 2021;82:575–80.CrossRefPubMed
16.
Shao YY, Guo Y, Feng XJ, Liu JJ, Chang ZP, Deng GF, et al. Oridonin attenuates TNBS-induced post-inflammatory irritable bowel syndrome via PXR/NF-kappaB signaling. Inflammation. 2021;44:645–58.CrossRefPubMed
17.
Xu M, Wan CX, Huang SH, Wang HB, Fan D, Wu HM, et al. Oridonin protects against cardiac hypertrophy by promoting P21-related autophagy. Cell Death Dis. 2019;10:403.CrossRefPubMedPubMedCentral
18.
He H, Jiang H, Chen Y, Ye J, Wang A, Wang C, et al. Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity. Nat Commun. 2018;9:2550.CrossRefPubMedPubMedCentral
19.
Du X, Que W, Hu X, Yu X, Guo WZ, Zhang S, et al. Oridonin prolongs the survival of mouse cardiac allografts by attenuating the NF-kappaB/NLRP3 pathway. Front Immunol. 2021;12:719574.CrossRefPubMedPubMedCentral
20.
Jia R, Yi Y, Liu J, Pei D, Hu B, Hao H, et al. Cyclic compression emerged dual effects on the osteogenic and osteoclastic status of LPS-induced inflammatory human periodontal ligament cells according to loading force. BMC Oral Health. 2020;20:7.CrossRefPubMedPubMedCentral
21.
Lundmark A, Hu YOO, Huss M, Johannsen G, Andersson AF, Yucel-Lindberg T. Identification of salivary microbiota and its association with host inflammatory mediators in periodontitis. Front Cell Infect Microbiol. 2019;9:216.CrossRefPubMedPubMedCentral
22.
Li C, Li B, Dong Z, Gao L, He X, Liao L, et al. Lipopolysaccharide differentially affects the osteogenic differentiation of periodontal ligament stem cells and bone marrow mesenchymal stem cells through Toll-like receptor 4 mediated nuclear factor kappaB pathway. Stem Cell Res Ther. 2014;5:67.CrossRefPubMedPubMedCentral
23.
24.
Sui BD, Hu CH, Liu AQ, Zheng CX, Xuan K, Jin Y. Stem cell-based bone regeneration in diseased microenvironments: challenges and solutions. Biomaterials. 2019;196:18–30.CrossRefPubMed
25.
Trubiani O, Pizzicannella J, Caputi S, Marchisio M, Mazzon E, Paganelli R, et al. Periodontal ligament stem cells: current knowledge and future perspectives. Stem Cells Dev. 2019;28:995–1003.CrossRefPubMed
26.
Tang J, Wu T, Xiong J, Su Y, Zhang C, Wang S, et al. Porphyromonas gingivalis lipopolysaccharides regulate functions of bone marrow mesenchymal stem cells. Cell Prolif. 2015;48:239–48.CrossRefPubMedPubMedCentral
27.
Zhou L, Dorfer CE, Chen L, Fawzy El-Sayed KM. Porphyromonas gingivalis lipopolysaccharides affect gingival stem/progenitor cells attributes through NF-kappaB, but not Wnt/beta-catenin, pathway. J Clin Periodontol. 2017;44:1112–22.CrossRefPubMed
28.
Vimalraj S. Alkaline phosphatase: structure, expression and its function in bone mineralization. Gene. 2020;754:144855.CrossRefPubMed
29.
Gregory CA, Gunn WG, Peister A, Prockop DJ. An Alizarin red-based assay of mineralization by adherent cells in culture: comparison with cetylpyridinium chloride extraction. Anal Biochem. 2004;329:77–84.CrossRefPubMed
30.
Alford AI, Kozloff KM, Hankenson KD. Extracellular matrix networks in bone remodeling. Int J Biochem Cell Biol. 2015;65:20–31.CrossRefPubMed
31.
32.
Han Y, You X, Xing W, Zhang Z, Zou W. Paracrine and endocrine actions of bone-the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts. Bone Res. 2018;6:16.CrossRefPubMedPubMedCentral
33.
Yang C, Wang Y, Liu H, Li N, Sun Y, Liu Z, et al. Ghrelin protects H9c2 cardiomyocytes from angiotensin II-induced apoptosis through the endoplasmic reticulum stress pathway. J Cardiovasc Pharmacol. 2012;59:465–71.CrossRefPubMed
34.
Hu H, Tian M, Ding C, Yu S. The C/EBP homologous protein (CHOP) transcription factor functions in endoplasmic reticulum stress-induced apoptosis and microbial infection. Front Immunol. 2018;9:3083.CrossRefPubMed
35.
Kim DS, Ha KC, Kwon DY, Kim MS, Kim HR, Chae SW, et al. Kaempferol protects ischemia/reperfusion-induced cardiac damage through the regulation of endoplasmic reticulum stress. Immunopharmacol Immunotoxicol. 2008;30:257–70.CrossRefPubMed
36.
Chaudhari AU, Byakod GN, Waghmare PF, Karhadkar VM. Correlation of levels of interleukin-1beta in gingival crevicular fluid to the clinical parameters of chronic periodontitis. J Contemp Dent Pract. 2011;12:52–9.CrossRefPubMed
37.
Wang Y, Chen L, Wei B, Wu X. Effects of oxymatrine on the activity of alkaline phosphatase in human periodontal ligament cells stimulated by porphyromonas gingivalis lipopolysaccharide. J Fujian Med Univ. 2017;51:166–9.
38.
Wu LY, Ye ZN, Zhuang Z, Gao Y, Tang C, Zhou CH, et al. Biochanin A reduces inflammatory injury and neuronal apoptosis following subarachnoid hemorrhage via suppression of the TLRs/TIRAP/MyD88/NF-kappaB pathway. Behav Neurol. 2018;2018:1960106.CrossRefPubMedPubMedCentral
39.
Liu QQ, Wang HL, Chen K, Wang SB, Xu Y, Ye Q, et al. Oridonin derivative ameliorates experimental colitis by inhibiting activated T-cells and translocation of nuclear factor-kappa B. J Dig Dis. 2016;17:104–12.CrossRefPubMed
Metadata
Title
Oridonin alleviates the inhibitory effect of lipopolysaccharide on the proliferation and osteogenic potential of periodontal ligament stem cells by inhibiting endoplasmic reticulum stress and NF-κB/NLRP3 inflammasome signaling
Authors
Junhao Jiang
Nong Zhang
Haibo Song
Ya Yang
Juan Li
Xiaoli Hu
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2023
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-023-02827-0

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