Critical roles of extracellular vesicles in periodontal disease and regeneration.

Extracellular vesicles (EVs) are evolutionarily conserved communication mediators that play key roles in the development of periodontal disease as well as in regeneration processes. This concise review first outlines the pathogenic mechanisms through which EVs derived from bacteria lead to the progression of periodontitis, with a focus on the enrichment of virulence factors, the amplification of immune responses, and the induction of bone destruction as key aspects influenced by bacterial EVs. This review aims to elucidate the positive effects of EVs derived from mesenchymal stem cells (MSC-EVs) on periodontal tissue regeneration.

SLC30A4-AS1 Mediates the Senescence of Periodontal Ligament Stem Cells in Inflammatory Environments via the Alternative Splicing of TP53BP1.

Periodontal ligament stem cells (PDLSCs) are key cells that suppress periodontal damage during both the progression and recovery stages of periodontitis. Although substantial evidence has demonstrated that incubation under an inflammatory condition may accelerate senescence of PDLSCs, whether cellular senescence in response to inflammatory incubation contributes to cell dysfunction remain unexplored. In this study, we first observed inflammation-caused PDLSC senescence in periodontitis based on comparisons of matched patients, and this cellular senescence was demonstrated in healthy cells that were subjected to inflammatory conditions.

Pyroptotic macrophages induce disruption of glutamate metabolism in periodontal ligament stem cells contributing to their compromised osteogenic potential.

Macrophage pyroptosis is of key importance to host defence against pathogen infections and may participate in the progression and recovery of periodontitis. However, the role of pyroptotic macrophages in regulating periodontal ligament stem cells (PDLSCs), the main cell source for periodontium renewal, remains unclear. First, we found that macrophage pyroptosis were enriched in gingiva tissues from periodontitis patients compared with those of healthy people through immunofluorescence.

Harnessing Mechanical Stress with Viscoelastic Biomaterials for Periodontal Ligament Regeneration.

The viscoelasticity of mechanically sensitive tissues such as periodontal ligaments (PDLs) is key in maintaining mechanical homeostasis. Unfortunately, PDLs easily lose viscoelasticity (e.g.

NADPH-dependent ROS accumulation contributes to the impaired osteogenic differentiation of periodontal ligament stem cells under high glucose conditions.

Diabetes mellitus is an established risk factor for periodontal disease that can aggravate the severity of periodontal inflammation and accelerate periodontal destruction. The chronic high glucose condition is a hallmark of diabetes-related pathogenesis, and has been demonstrated to impair the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), leading to delayed recovery of periodontal defects in diabetic patients. Reactive oxygen species (ROS) are small molecules that can influence cell fate determination and the direction of cell differentiation.

Biotin-Avidin System-Based Delivery Enhances the Therapeutic Performance of MSC-Derived Exosomes.

Exosomes (EXs) shed by mesenchymal stem cells (MSCs) are potent therapeutic agents that promote wound healing and regeneration, but when used alone , their therapeutic potency is diminished by rapid clearance and bioactivity loss. Inspired by the biotin-avidin interaction, we developed a simple yet versatile method for the immobilization of MSC-derived EXs (MSC-EXs) into hydrogels and achieved sustained release for regenerative purposes. First, biotin-modified gelatin methacryloyl (Bio-GelMA) was fabricated by grafting NHS-PEG-biotin onto the amino groups of GelMA.

Long non-coding RNA AC018926.2 regulates palmitic acid exposure-compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway.

Although obesity has been proposed as a risk factor for periodontitis, the influence of excessive fat accumulation on the development of periodontitis and periodontal recovery from disease remains largely unknown. This study investigated the cellular response of periodontal ligament stem cells (PDLSCs) to elevated levels of a specific fatty acid, namely, palmitic acid (PA). The mechanism by which PA exposure compromises the osteogenic potential of cells was also explored.

Roles of extracellular vesicles in periodontal homeostasis and their therapeutic potential.

Periodontal tissue is a highly dynamic and frequently stimulated area where homeostasis is easily destroyed, leading to proinflammatory periodontal diseases. Bacteria-bacteria and cell-bacteria interactions play pivotal roles in periodontal homeostasis and disease progression. Several reviews have comprehensively summarized the roles of bacteria and stem cells in periodontal homeostasis.

Gold nanoparticles targeting the autophagy-lysosome system to combat the inflammation-compromised osteogenic potential of periodontal ligament stem cells: From mechanism to therapy.

Although substantial data indicate that the osteogenic potential of periodontal ligament stem cells (PDLSCs) is compromised under inflammatory conditions, the underlying mechanism remains largely unexplored. In this study, we found that both the autophagy levels and autophagic flux levels were decreased in PDLSCs incubated under inflammatory conditions (I-PDLSCs). Based on the increased expression of LC3 II (at an autophagy level) and decreased accumulation of LC3 II (at an autophagic flux level) in I-PDLSCs, we speculated that the disruption of I-PDLSC autophagy arose from dysfunction of the cellular autophagy-lysosome system.

Metformin combats high glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells via inhibition of the NPR3-mediated MAPK pathway.

Background: High glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) has long been a challenge to periodontal regeneration for diabetic individuals. Metformin is an anti-hyperglycemic drug that exhibits abundant biological activities associated with cell metabolism and downstream tissue regeneration. However, how metformin combats damage to PDLSC osteogenic differentiation under high glucose and the underlying mechanisms remain unknown.

LncRNA GACAT2 binds with protein PKM1/2 to regulate cell mitochondrial function and cementogenesis in an inflammatory environment.

Periodontal ligament stem cells (PDLSCs) are a key cell type for restoring/regenerating lost/damaged periodontal tissues, including alveolar bone, periodontal ligament and root cementum, the latter of which is important for regaining tooth function. However, PDLSCs residing in an inflammatory environment generally exhibit compromised functions, as demonstrated by an impaired ability to differentiate into cementoblasts, which are responsible for regrowing the cementum. This study investigated the role of mitochondrial function and downstream long noncoding RNAs (lncRNAs) in regulating inflammation-induced changes in the cementogenesis of PDLSCs.

Role of molybdenum in material immunomodulation and periodontal wound healing: Targeting immunometabolism and mitochondrial function for macrophage modulation.

Recently, strategies that can target the underlying mechanisms of phenotype change to modulate the macrophage immune response from the standpoint of biological science have attracted increasing attention in the field of biomaterials. In this study, we printed a molybdenum-containing bioactive glass ceramic (Mo-BGC) scaffold as an immunomodulatory material. In a clinically relevant critical-size periodontal defect model, the defect-matched scaffold featured robust immunomodulatory activity, enabling long-term stable macrophage modulation and leading to enhanced regeneration of multiple periodontal tissues in canines.

Periodontitis-compromised dental pulp stem cells secrete extracellular vesicles carrying miRNA-378a promote local angiogenesis by targeting Sufu to activate the Hedgehog/Gli1 signalling.

Objectives: Previously, our investigations demonstrated robust pro-angiogenic potentials of extracellular vesicles secreted by periodontitis-compromised dental pulp stem cells (P-EVs) when compared to those from healthy DPSCs (H-EVs), but the underlying mechanism remains unknown.

Materials And Methods: Here, circulating microRNAs (miRNAs) specifically found in P-EVs (compared with H-EVs) were identified by Agilent miRNA microarray analysis, and the roles of the candidate miRNA in P-EV-enhanced cell angiogenesis were confirmed by cell transfection and RNA interference methods. Next, the direct binding affinity between the candidate miRNA and its target gene was evaluated by luciferase reporter assay.

Exosomes derived from M0, M1 and M2 macrophages exert distinct influences on the proliferation and differentiation of mesenchymal stem cells.

Background: Different phenotypes of macrophages (M0, M1 and M2 Mφs) have been demonstrated to play distinct roles in regulating mesenchymal stem cells in various in vitro and in vivo systems. Our previous study also found that cell-conditioned medium (CM) derived from M1 Mφs supported the proliferation and adipogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs), whereas CM derived from either M0 or M2 Mφs showed an enhanced effect on cell osteogenic differentiation. However, the underlying mechanism remains incompletely elucidated.

Suppression of histone deacetylases by SAHA relieves bone cancer pain in rats via inhibiting activation of glial cells in spinal dorsal horn and dorsal root ganglia.

Background: Robust activation of glial cells has been reported to occur particularly during the pathogenesis of bone cancer pain (BCP). Researchers from our group and others have shown that histone deacetylases (HDACs) play a significant role in modulating glia-mediated immune responses; however, it still remains unclear whether HDACs are involved in the activation of glial cells during the development of BCP.

Methods: BCP model was established by intra-tibia tumor cell inoculation (TCI).

The proangiogenic effects of extracellular vesicles secreted by dental pulp stem cells derived from periodontally compromised teeth.

Background: Although dental pulp stem cells (DPSCs) isolated from periodontally compromised teeth (P-DPSCs) have been demonstrated to retain pluripotency and regenerative potential, their use as therapeutics remains largely unexplored. In this study, we investigated the proangiogenic effects of extracellular vesicles (EVs) secreted by P-DPSCs using in vitro and in vivo testing models.

Methods: Patient-matched DPSCs derived from periodontally healthy teeth (H-DPSCs) were used as the control for P-DPSCs.

Surface modification via plasmid-mediated pLAMA3-CM gene transfection promotes the attachment of gingival epithelial cells to titanium sheets in vitro and improves biological sealing at the transmucosal sites of titanium implants in vivo.

Although titanium implants have been applied in dental clinics to replace lost teeth and to restore masticatory function for decades, strategies to design the surface of the transmucosal sites of implants to achieve ideal and predictable biological sealing following implantation remain to be optimized. In this study, we hypothesized that gingival epithelial cell (GEC) adhesion and new tissue attachment to titanium sheets/implants could be promoted by the release of plasmid pLAMA3-CM (encoding a motif of the C-terminal globular domain of LAMA3) from a titanium surface. To test this hypothesis, a chitosan/collagen (Chi/Col) coating was immobilized on the surfaces of titanium substrates with nanotube topography (NT-Ti) through cathodic electrophoretic deposition; it was found that pLAMA3-CM could be released from the coating in a highly sustained manner.

[The protective effects of vitamin E on lung injury caused by high temperature and PM in COPD rats].

Objective: To investigate the effects of vitamin E on the respiratory function impairment in rats with chronic obstructive pulmonary disease (COPD) after exposed to high temperature and PM.

Methods: Fifty-four 7-week-old SPF male Wistar rats were randomly divided into 9 experimental groups (n=6). The rat COPD model was established by lipopolysaccharide (LPS) and smoke exposure.

M2 Macrophages Enhance the Cementoblastic Differentiation of Periodontal Ligament Stem Cells via the Akt and JNK Pathways.

Although macrophage (Mφ) polarization has been demonstrated to play crucial roles in cellular osteogenesis across the cascade of events in periodontal regeneration, how polarized Mφ phenotypes influence the cementoblastic differentiation of periodontal ligament stem cells (PDLSCs) remains unknown. In the present study, human monocyte leukemic cells (THP-1) were induced into M0, M1, and M2 subsets, and the influences of these polarized Mφs on the cementoblastic differentiation of PDLSCs were assessed in both conditioned medium-based and Transwell-based coculture systems. Furthermore, the potential pathways and cyto-/chemokines involved in Mφ-mediated cementoblastic differentiation were screened and identified.