Necrostatin-1 promotes ectopic periodontal tissue like structure regeneration in LPS-treated PDLSCs

Yan, Bingbing; Zhang, Hongmei; Dai, Taiqiang; Gu, Yongchun; Qiu, Xinyu; Hu, Cheng; Liu, Yan; Wei, Kewen; Li, Dehua

doi:10.1371/journal.pone.0207760

Cited by 19 publications

(13 citation statements)

References 20 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cells (1 × 10 5 ) were seeded in six‐well plates and divided into the following six groups: the control group, Pg‐LPS treatment group (LPS), group MI, TAK‐242 treatment group (TAK), MI and Pg‐LPS treatment group (MI + LPS), and MI and Pg‐LPS plus TAK‐242 treatment group (MI + LPS + TAK). The concentration of Pg‐LPS was 10 µg/mL as described by Bingbing Yan 18 . The MI medium contained 10% fetal bovine serum, 50 mg/mL ascorbic acid, 10 mM β‐glycerophosphate, and 100 nM dexamethasone.…”

Section: Methodsmentioning

confidence: 99%

The role of PHF8 and TLR4 in osteogenic differentiation of periodontal ligament cells in inflammatory environment

Liu

et al. 2020

Journal of Periodontology

View full text Add to dashboard Cite

Background: Histone methylation is considered to play an important role in the occurrence and development of periodontitis. Plant homeodomain finger protein 8 (PHF8), a histone demethylase, has been shown to regulate inflammation and osteogenic differentiation of bone marrow stromal cells (BMSCs). This study aimed to detect the functions of PHF8 and TLR4 in osteogenic differentiation in an inflammatory environment induced by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) Methods: A periodontitis mouse model was established, and the mice were treated with TAK-242. Immunohistochemical staining was used to detect the expression of PHF8 in periodontal tissue. Periodontal ligament cells (PDLCs) were treated with mineralization induction medium supplemented with Pg-LPS and/or TAK-242, and a Cell Counting Kit-8 (CCK-8) assay was used to detect the proliferation of PDLCs. Real-time PCR and western blotting were used to detect the mRNA and protein expression levels, respectively, of PHF8, toll-like receptor 4 (TLR4) and the other osteogenic markers alkaline phosphatase (ALP), osteocalcin (OCN), Special AT-rich sequence-binding protein 2 (Satb2) and Runt-related transcription factor 2 (Runx2) Results: Periodontitis reduced PHF8 expression in periodontal tissue, and TAK-242 partially reversed this downregulation. An in vitro experiment revealed that the mRNA and protein expression levels of PHF8 were significantly upregulated during the osteogenic differentiation of PDLCs. Alizarin red staining showed that the mineralized nodules of PDLCs in osteogenic induction group were more than those in control group. Real-time PCR and western blot results indicated that Pg-LPS inhibited PHF8 expression and upregulated TLR4 expression in PDLCs.TAK-242 inhibited TLR4 and partially reversed the inhibition of PHF8 expression and osteogenic differentiation induced by Pg-LPS in PDLCs Conclusion: PHF8 and TLR4 play important roles in periodontitis. Pg-LPS inhibits the expression of PHF8 via upregulation of TLR4 and might further inhibit the osteogenic differentiation of PDLCs. However, the specific mechanisms involved remain to be explored.

show abstract

Section: Methodsmentioning

confidence: 99%

The role of PHF8 and TLR4 in osteogenic differentiation of periodontal ligament cells in inflammatory environment

Liu

et al. 2020

Journal of Periodontology

View full text Add to dashboard Cite

show abstract

“…Periodontitis, characterized by tooth mobility and bleeding from gingiva, is a chronic inflammatory disease that causes gingival detachment and disintegration of alveolar bone [1]. It was recently reported that periodontitis broadly affects up to 50% of adults [2]. Previous studies have demonstrated periodontitis is related to systemic conditions such as cardiovascular disease, diabetes mellitus, adverse pregnancy outcomes, and osteoporosis [3].…”

Section: Introductionmentioning

confidence: 99%

Salvianolic Acid C Attenuates LPS-Induced Inflammation and Apoptosis in Human Periodontal Ligament Stem Cells via Toll-Like Receptors 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Pathway

Duan¹,

An²,

Wu³

et al. 2019

Med Sci Monit

View full text Add to dashboard Cite

BackgroundPeriodontitis is a chronic inflammatory disease that causes gingival detachment and disintegration of alveolar bone. Salvianolic acid C (SAC) is a polyphenol compound with anti-inflammatory and antioxidant activities that is isolated from Danshen, a traditional Chinese medicine made from the roots of Salvia miltiorrhiza Bunge. The aim of this study was to investigate the mechanisms of underlying its protective effects and its inhibition effect on inflammation and apoptosis in human periodontal ligament stem cells (hPDLSCs).Material/MethodsLPS-induced hPDLSCs, as a model mimicking an inflammatory process of periodontitis in vivo, were established to investigate the therapeutic effect of SAC in periodontitis. The inflammatory cytokines secretion and oxidative stress status were measured by use of specific commercial test kits. The hPDLSCs viability was analyzed by Cell Counting Kit-8 assay. The cell apoptosis and cell cycle were assayed with flow cytometry. Expressions levels of proteins involved in apoptosis, osteogenic differentiation, and TLR4/NF-κB pathway were evaluated by Western blotting. Alkaline phosphatase (ALP) activity was detected by ALP assay kit and ALP staining. The mineralized nodules formation of hPDLSCs was checked by Alizarin Red S staining.ResultsOur results showed that LPS induced increased levels of inflammatory cytokines and oxidative stress and mediated the phosphorylation and nuclear translocation of NF-κB p65 in hPDLSCs. SAC reversed the abnormal secretion of inflammatory cytokines and inhibited the TLR4/NF-κB activation induced by LPS. SAC also upregulated cell viability, ALP activity, and the ability of osteogenic differentiation. The anti-inflammation and TLR4/NF-κB inhibition effects of SAC were reversed by TLR4 overexpression.ConclusionsTaken together, our results revealed that SAC effectively attenuates LPS-induced inflammation and apoptosis via the TLR4/NF-κB pathway and that SAC is effective in treating periodontitis.

show abstract

“…Periodontal ligament stem cells are the core examinee stem cells for periodontal regeneration. Due to their self-renewal potential and multidifferentiation capability, PDLSCs have been widely used in tissue regeneration including periodontium [16]. The function and fate of PDLSCs are closely associated with the pathogenesis, progression, treatment, and prognosis in periodontitis [17,18].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Endoplasmic Reticulum Stress by 4-Phenyl Butyric Acid Presents Therapeutic Effects on Periodontitis: Experimental Studies In Vitro and in Rats

Yang

Zhang

Wang

et al. 2021

Stem Cells International

View full text Add to dashboard Cite

This study investigated the probable mechanisms of endoplasmic reticulum (ER) stress involved in periodontitis in vitro and in vivo. We isolated periodontal ligament stem cells from periodontitis patients and healthy controls (P-PDLSCs and H-PDLSCs). To further simulate the periodontal microenvironment in patients, lipopolysaccharide (LPS) was used to treat H-PDLSCs. The results showed that periodontitis-related inflammation gave rise to the upregulated expression levels of ER stress representative genes including GRP78, PERK, ATF4, and CHOP. In contrast, the treatment of 4-phenyl butyric acid (4-PBA) remarkably suppressed ER stress and supported cell viability. The increased secretion of proinflammatory factors like TNF-α, IL-1β, and IL-6 and the activation of NF-κB pathway were also attenuated by 4-PBA treatment. Moreover, 4-PBA treatment restored the impaired osteogenic differentiation ability of PDLSCs, as demonstrated by the upregulated expression levels of Runx2 and OCN as well as the enhanced Alizarin red staining. Local administration of 4-PBA could rescue alveolar bone resorption of LPS-induced periodontitis rats. Thus, our findings suggested ER stress might act as a promising therapeutic target against periodontitis.

show abstract

Necrostatin-1 promotes ectopic periodontal tissue like structure regeneration in LPS-treated PDLSCs

Cited by 19 publications

References 20 publications

The role of PHF8 and TLR4 in osteogenic differentiation of periodontal ligament cells in inflammatory environment

The role of PHF8 and TLR4 in osteogenic differentiation of periodontal ligament cells in inflammatory environment

Salvianolic Acid C Attenuates LPS-Induced Inflammation and Apoptosis in Human Periodontal Ligament Stem Cells via Toll-Like Receptors 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Pathway

Inhibition of Endoplasmic Reticulum Stress by 4-Phenyl Butyric Acid Presents Therapeutic Effects on Periodontitis: Experimental Studies In Vitro and in Rats

Contact Info

Product

Resources

About