Maresin-1 and Resolvin E1 Promote Regenerative Properties of Periodontal Ligament Stem Cells Under Inflammatory Conditions

Albuquerque‐Souza, Emmanuel; Schulte, Fabian; Chen, Tsute; Hardt, Markus; Hastürk, Hatice; Dyke, Thomas E. Van; Holzhausen, Marinella; Kantarcı, Alpdoğan

doi:10.3389/fimmu.2020.585530

Cited by 48 publications

(41 citation statements)

References 79 publications

(101 reference statements)

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“…The ability of RvE4 to limit neutrophil tissue infiltration and to enhance efferocytosis are also functions shared by other members of the E-series resolvins ( Table 1 ). For example, RvE1’s pro-resolving actions include stopping neutrophil ( 12 , 14 , 37 – 39 ) and dendritic cell migration ( 11 , 40 ), reducing pro-inflammatory cytokines ( 41 ), enhancing macrophage phagocytosis and efferocytosis ( 37 , 38 ), enhancing bacterial clearance ( 41 ), modulating T cell responses ( 42 ) and regenerating periodontal ligament stem cells ( 43 ). RvE1 has unique actions on platelets by inhibiting adenosine diphosphate (ADP)-activated mobilization of P-selectin to minimize platelet aggregation.…”

Section: Discussionmentioning

confidence: 99%

A New E-Series Resolvin: RvE4 Stereochemistry and Function in Efferocytosis of Inflammation-Resolution

et al. 2021

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The resolution of the acute inflammatory response is governed by phagocytes actively clearing apoptotic cells and pathogens. Biosynthesis of the specialized pro-resolving mediators (SPMs) is pivotal in the resolution of inflammation via their roles in innate immune cells. Resolvin E4 (RvE4: 5S,15S-dihydroxy-eicosapentaenoic acid) is a newly uncovered member of the E-series resolvins biosynthesized from eicosapentaenoic acid (EPA) recently elucidated in physiologic hypoxia. This new resolvin was termed RvE4 given its ability to increase efferocytosis of apoptotic cells by macrophages. Herein, we report on the total organic synthesis of RvE4 confirming its unique structure, complete stereochemistry assignment and function. This synthetic RvE4 matched the physical properties of biogenic RvE4 material, i.e. ultra-violet (UV) absorbance, chromatographic behavior, and tandem mass spectrometry (MS2) fragmentation, as well as bioactivity. We confirmed RvE4 potent responses with human M2 macrophage efferocytosis of human apoptotic neutrophils and senescent red blood cells. Together, these results provide direct evidence for the assignment of the complete stereochemistry of RvE4 as 5S,15S-dihydroxy-6E,8Z,11Z,13E,17Z-eicosapentaenoic acid and its bioactions in human phagocyte response.

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Section: Discussionmentioning

confidence: 99%

A New E-Series Resolvin: RvE4 Stereochemistry and Function in Efferocytosis of Inflammation-Resolution

et al. 2021

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“…Resolvins are known to resolve inflammation, stimulate periodontal tissue healing and regenerate lost alveolar bone. RvE1 induces periodontal regeneration in pre-clinical periodontitis models ( 12 – 14 , 59 , 60 ), promotes regenerative properties of periodontal ligament (PDL) stem cells ( 61 ), and regulates osteoclasts as well as osteoblasts favorably for bone preservation ( 62 – 64 ). RvE3 demonstrates potent resolution properties by limiting neutrophil infiltration in the peritonitis model and inhibiting neutrophil chemotaxis ( 65 – 67 ).…”

Section: Discussionmentioning

confidence: 99%

“…Maresins can promote periodontal tissue healing and regulate periodontal inflammation. MaR1 promotes survival and inhibits apoptosis in PDL cells ( 71 ), induces regenerative properties of PDL stem cells ( 61 ), and restores phagocytic capacity of macrophages from periodontitis patients ( 72 ). Both RvD1 and RvE3 were highly correlated with multiple bacterial species in periodontitis after treatment suggesting their important role in resolution of periodontal inflammation associated with subgingival microbiota shift.…”

Section: Discussionmentioning

confidence: 99%

Subgingival Microbiome and Specialized Pro-Resolving Lipid Mediator Pathway Profiles Are Correlated in Periodontal Inflammation

Lee

Zhu

et al. 2021

Front. Immunol.

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Failure of resolution pathways in periodontitis is reflected in levels of specialized pro-resolving lipid mediators (SPMs) and SPM pathway markers but their relationship with the subgingival microbiome is unclear. This study aimed to analyze and integrate lipid mediator level, SPM receptor gene expression and subgingival microbiome data in subjects with periodontitis vs. healthy controls. The study included 13 periodontally healthy and 15 periodontitis subjects that were evaluated prior to or after non-surgical periodontal therapy. Samples of gingival tissue and subgingival plaque were collected prior to and 8 weeks after non-surgical treatment; only once in the healthy group. Metabololipidomic analysis was performed to measure levels of SPMs and other relevant lipid mediators in gingiva. qRT-PCR assessed relative gene expression (2-ΔΔCT) of known SPM receptors. 16S rRNA sequencing evaluated the relative abundance of bacterial species in subgingival plaque. Correlations between lipid mediator levels, receptor gene expression and bacterial abundance were analyzed using the Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) and Sparse Partial Least Squares (SPLS) methods. Profiles of lipid mediators, receptor genes and the subgingival microbiome were distinct in the three groups. The strongest correlation existed between lipid mediator profile and subgingival microbiome profile. Multiple lipid mediators and bacterial species were highly correlated (correlation coefficient ≥0.6) in different periodontal conditions. Comparing individual correlated lipid mediators and bacterial species in periodontitis before treatment to healthy controls revealed that one bacterial species, Corynebacterium durum, and five lipid mediators, 5(S)6(R)-DiHETE, 15(S)-HEPE, 7-HDHA, 13-HDHA and 14-HDHA, were identified in both conditions. Comparing individual correlated lipid mediators and bacterial species in periodontitis before treatment to after treatment revealed that one bacterial species, Anaeroglobus geminatus, and four lipid mediators, 5(S)12(S)-DiHETE, RvD1, Maresin 1 and LTB4, were identified in both conditions. Four Selenomonas species were highly correlated with RvD1, RvE3, 5(S)12(S)-DiHETE and proinflammatory mediators in the periodontitis after treatment group. Profiles of lipid mediators, receptor gene and subgingival microbiome are associated with periodontal inflammation and correlated with each other, suggesting inflammation mediated by lipid mediators influences microbial composition in periodontitis. The role of correlated individual lipid mediators and bacterial species in periodontal inflammation have to be further studied.

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“…Considering the variations of the effects of PDLSC-CM among donor’s teeth, we used PDLSC-CMs taken from three PDLSC lines for each experiment in this study [ 22 , 23 , 24 ]. In order to establish PDLSC lines, PDL tissue was collected from 8 extracted premolars of healthy volunteers (14–28 years old, average 18 years old, 1 male, and 7 females).…”

Section: Methodsmentioning

confidence: 99%

Angiogenic Effects of Secreted Factors from Periodontal Ligament Stem Cells

et al. 2021

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Periodontal disease is a chronic inflammation of tooth-supporting tissues, and the destruction of these tissues results in tooth loss. Regeneration of periodontal tissues is the ultimate goal of periodontal treatment. We previously reported that transplantation of conditioned medium (CM) of periodontal ligament stem cells (PDLSCs) demonstrated the enhancement of periodontal tissue regeneration, compared to CM from fibroblasts (Fibroblast-CM). We hypothesized that the angiogenic effects of PDLSC-CM might participate in the enhanced wound healing of periodontal tissues. The aim of this study was to investigate the effect of PDLSC-CM on the functions of endothelial cells. PDLSCs were cultured from periodontal ligament tissues obtained from healthy volunteers. Human gingival epithelial cells, dermal fibroblasts, osteoblasts, and umbilical vein endothelial cells (HUVECs) were purchased from commercial sources. The functions of endothelial cells were examined using immunostaining of Ki67, observation of nuclear fragmentation and condensation (apoptosis), and network formation on Matrigel. Vascular endothelial cell growth factor (VEGF) level was measured using an ELISA kit. HUVECs demonstrated higher cell viability in PDLSC-CM when compared with those in Fibroblast-CM. HUVECs demonstrated a higher number of Ki67-positive cells and lower apoptosis cells in PDLSC-CM, compared to Fibroblast-CM. Additionally, HUVECs formed more capillary-like structures in PDLSC-CM than Fibroblast-CM. PDLSC-CM contained higher levels of angiogenic growth factor, VEGF, than Fibroblast-CM. Our results showed that PDLSC-CM increased cell viability, proliferation, and capillary formation of HUVECs compared to Fibroblast-CM, suggesting the angiogenic effects of PDLSC-CM, and the effect is a potential regenerative mechanism of periodontal tissues by PDLSC-CM.

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Maresin-1 and Resolvin E1 Promote Regenerative Properties of Periodontal Ligament Stem Cells Under Inflammatory Conditions

Cited by 48 publications

References 79 publications

A New E-Series Resolvin: RvE4 Stereochemistry and Function in Efferocytosis of Inflammation-Resolution

A New E-Series Resolvin: RvE4 Stereochemistry and Function in Efferocytosis of Inflammation-Resolution

Subgingival Microbiome and Specialized Pro-Resolving Lipid Mediator Pathway Profiles Are Correlated in Periodontal Inflammation

Angiogenic Effects of Secreted Factors from Periodontal Ligament Stem Cells

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