Progranulin is highly expressed in patients with chronic periodontitis and protects against experimental periodontitis in rats

Xiao, Li; Zuo, Zhibin; Chen, Qian; Li, Jing; Tang, Wei; Yang, Pishan

doi:10.1002/jper.18-0132

Cited by 11 publications

(17 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the mechanism and specific role of TNFRs in PGRN mediated inhibition of M1 polarization remains to be explored. Besides, though we have shown that PGRN protects against experimental periodontitis [30] and promotes inflammatory periodontal bone defect regeneration in rats [31], whether this in vivo efficacy of PGRN is related to anti-M1 polarization waits for investigation.…”

Section: Discussionmentioning

confidence: 91%

“…Plenty of studies indicate that macrophages, when as M1 phenotype, play a vital role in onset and development of periodontitis [34], while PGRN, identified as an endogenous antagonist of TNF-α by competitively binding to TNFRs, has potential positive action in autoimmune and inflammatory diseases, such as osteoarthritis [35] and periodontitis [30]. In this study, we demonstrated that rPGRN inhibited LPS-induced macrophage M1 polarization and these effects were associated with NF-кB and MAPK pathway inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, PGRN has been demonstrated to have the protective role in osteoarthritis [23,25], inflammatory bowel disease [26], psoriasis [27], and various autoimmune diseases [28,29]. Our previous studies demonstrate that PGRN is highly expressed in periodontitis tissues such as the gingiva and gingival crevicular fluid and recombinant PGRN plays protective role in experimental periodontitis in rats [30] and promotes inflammatory periodontal bone defect regeneration in rats by inhibition of inflammation and osteoclast and promotion of osteogenesis [31]. However, the role of PGRN in modulating macrophage function has been seldom investigated [32].…”

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Macrophage M1 polarization plays a pivotal role in inflammatory diseases. Progranulin (PGRN) has potential anti-inflammation action, however, the effect of PGRN on macrophage M1 polarization has been poorly studied. Our study aimed to investigate the effect of PGRN on lipopolysaccharide (LPS)-induced macrophage M1 polarization and clarify the underlying mechanisms. Methods: RAW264.7 cells were polarized to M1 macrophage by LPS with or without recombinant PGRN (rPGRN) and tumor necrosis factor alpha antibody (anti-TNF-α). A cell counting kit-8 assay (CCK-8), flow cytometry, Quantitative Real-Time PCR assay (q-PCR), Western blot assay and enzyme-linked immunosorbent assay (ELISA) were used to determine the effect of different treatments on cell proliferation, expression of surface phenotype marker and expressions and secretion of inflammatory cytokines. The activation of NF-κB/mitogen-activated protein kinase (MAPK) pathways and the nuclear translocation of NF-κB p65 were detected by Western blot and immunofluorescence respectively. THP-1 and primary bone marrow-derived monocytes (BMDMs) were also used to demonstrate effect of PGRN on expressions and secretion of inflammatory cytokines induced by LPS. Results: In RAW264.7 cells, rPGRN at concentrations below 80 ng/ml significantly promoted cell proliferation in dose dependent fashion. rPGRN significantly inhibited LPS-induced change of phenotype (CD86/CD206 ratio) and function (tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) expressions). LPS-stimulated secretion of TNF-α and activated phosphorylation of IKKα/β, IкBα, p65, JNK and p38 and the nucleus translocation of NF-кB p65 were also significantly downregulated by rPGRN. In addition, recombinant TNF-α (rTNF-α) significantly boosted TNF-α and iNOS expression vs the control group. Moreover, anti-TNF-α significantly inhibited LPS-induced TNF-α and iNOS expression. In THP-1 and BMDM cells, reversing effect of rPGRN on LPS-enhanced expressions of TNF-α and iNOS and secretion of TNF-α was further demonstrated.

show abstract

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Patients were recruited from April 2018 to August 2018 in Cangzhou Central Hospital. CP patients were selected strictly following the criteria described previously by Li et al 20 All the patients were age ≥ 21 years and the presence of at least 20 teeth. CP patients should have multiple sites with a probing depth (PD) of ≥ 5 mm, attachment loss (AL) of ≥ 2 mm and bone loss confirmed by radiography.…”

Section: Methodsmentioning

confidence: 99%

Beneficial Effects of Glycyrrhizin in Chronic Periodontitis Through the Inhibition of Inflammatory Response

Sun

Zhao

et al. 2020

Dose-Response

View full text Add to dashboard Cite

Elevated inflammatory cytokines and high mobility group box 1 (HMGB1) production are associated with chronic periodontitis (CP). Glycyrrhizin is the major constituent of Glycyrrhiza glabra. L. (Fabaceae) root with anti-inflammation activities. This study evaluated the effects of glycyrrhizin on CP. TNF-α-treated human periodontal ligament stem cell (hPDLSC) model was established, and was administrated with 1, 2 or 5 mM glycyrrhizin for 24 h. After treatment, the expression of HMGB1and inflammatory cytokines was monitored. Significantly increased HMGB1 (median: 5646.4, range: 1918.2-8233.7 vs median: 204.5, range: 98.7-283.6, pg/mL), TNF-α (median: 345.5, range: 161.0-567.9 vs median: 93.5, range: 58.1-159.3, pg/mL), IL-1β (median: 2014.6, range: 209.5-4308.1 vs median: 224.5, range: 48.8-335.8, pg/mL) and IL-6 (median: 1223.6, range: 398.2-2183.8 vs median: 240.4, range: 105.2-400.5, pg/mL) were detected in gingival crevicular fluid from CP patients. Glycyrrhizin significantly prevented TNF-α-induced expression of HMGB1 (691.5 ± 136.4 vs 142.8 ± 57.3 pg/mL), IL-6 (388.1 ± 85.2 vs 189.4 ± 61.2 pg/mL) and IL-1β (176.3 ± 47.2 vs 53.9 ± 25.7 pg/mL) in hPDLSC. In CP rats, glycyrrhizin significantly decreased HMGB1 (5795.6 ± 1121.5 vs 586.4 ± 436.8 pg/mL), TNF-α (421.8 ± 93.7 vs 87.9 ± 21.6 pg/mL), IL-6 (1423.8 ± 235.2 vs 622.6 ± 176.1 pg/mL) and IL-1β (1562.8 ± 334.3 vs 733.5 ± 265.1 pg/mL) in gingival crevicular fluid. Glycyrrhizin suppresses inflammatory activities in CP rats and represents a promising molecule for controlling CP.

show abstract

“…However, anti‐inflammation and osteogenesis promotion by PGRN in periodontitis condition has been seldom investigated. Our recent studies indicated that PGRN was highly expressed in the gingiva and gingival crevicular fluid of patients with chronic periodontitis and exogenous PGRN could protect against experimental periodontitis in rats ; and PGRN could promote regeneration of inflammatory periodontal bone defect in rats via anti‐inflammation, osteoclastogenic inhibition, and osteogenic promotion . For deeper insight of the underlying mechanism of PGRN in improving periodontal regeneration, the present study was conducted to investigate the role of TNFR1 and TNFR2 as well as the underlying signaling pathways in the process of hPDLSCs osteogenic differentiation promoted by PGRN with or without TNF‐α stimulation.…”

Section: Introductionmentioning

confidence: 97%

Progranulin promotes osteogenic differentiation of human periodontal ligament stem cells via tumor necrosis factor receptors to inhibit TNF‐α sensitized NF‐kB and activate ERK/JNK signaling

Chen

et al. 2019

J of Periodontal Research

Self Cite

View full text Add to dashboard Cite

Objective: To investigate the molecular mechanism of Progranulin (PGRN) in promoting osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in inflammatory environment. Background:Progranulin is an antagonist of tumor necrosis factor (TNF) receptors (TNFRs) and is known to promote inflammatory periodontal bone defect regeneration.Methods: TNFR1-and TNFR2-silenced hPDLSCs designed as hPDLSCs-sh-TNFR1 and hPDLSCs-sh-TNFR2 were cultured with osteoinductive medium containing TNF-α and (or) PGRN. Immunofluorescence, quantitative real-time PCR, and western blot were used to, respectively, detect expressions of TNFR1\TNFR2 and osteogenic differentiation markers as well as phosphorylation level in NF-κB\MAPK-related pathways. Results: Immunofluorescence and real-time PCR showed that TNFR1 and TNFR2 positively expressed in hPDLSCs. TNF-α stimulation could significantly decrease the expressions of ALP and RUNX2 in hPDLSCs, whereas PGRN treatment could significantly enhance their expressions, and reverse TNF-α-mediated expression suppression of ALP and RUNX2 in hPDLSCs. In hPDLSCs-sh-TNFR1, TNF-α mediated osteogenic inhibition decreased, but both TNF-α + PGRN and alone PGRN significantly promoted expression of ALP and RUNX2. PGRN significantly enhanced expression of P-ERK1/2 and P-JNK, while corresponding inhibitors eliminated PGRN-stimulated osteogenic differentiation. In hPDLSCssh-TNFR2, no significant difference existed in osteogenic markers and P-JNK expression between the PGRN group and the control group. However, PGRN still activated P-ERK1/2 expression. Besides, PGRN antagonized TNF-α-enhanced NF-κB P65 expression. Conclusion: Progranulin promotes osteogenic differentiation of hPDLSCs via TNFR1to inhibit TNF-α-sensitized NF-κB and via TNFR2 to activate JNK signaling. The mechanism by which PGRN activates ERK signaling remains to be explored.

show abstract

Progranulin is highly expressed in patients with chronic periodontitis and protects against experimental periodontitis in rats

Abstract: These findings suggest that progranulin is highly expressed in the gingiva and GCF of patients with CP and protects against experimental periodontitis in rats.

Cited by 11 publications

References 42 publications

Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways

Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways

Beneficial Effects of Glycyrrhizin in Chronic Periodontitis Through the Inhibition of Inflammatory Response

Progranulin promotes osteogenic differentiation of human periodontal ligament stem cells via tumor necrosis factor receptors to inhibit TNF‐α sensitized NF‐kB and activate ERK/JNK signaling

Contact Info

Product

Resources

About