ASC-expressing pyroptotic extracellular vesicles alleviate sepsis by protecting B cells.

Pyroptosis is an inflammatory programmed cell death process characterized by membrane rupture. Interestingly, pyroptotic cells can generate plenty of nanosized vesicles. Non-inflammatory apoptotic cell death-derived apoptotic vesicles (apoVs) were systemically characterized and displayed multiple physiological functions and therapeutic potentials. However, the characteristics of pyroptotic cell-generated extracellular vesicles (EVs) are largely unknown. Here, we identified a group of pyroptotic EVs (pyroEVs) from in vitro cultured pyroptotic mesenchymal stem cells (MSCs), as well as from septic mouse blood. Compared with apoVs, pyroEVs express similar levels of annexin V, calreticulin, and common EV markers, but express a decreased level of apoptotic marker cleave caspase-3. PyroEVs, but not apoVs and exosomes, specifically express pyroptotic maker apoptosis-associated speck-like protein containing CARD (ASC). More importantly, MSC-derived pyroEVs protect B cells in the spleen and bone marrow to relieve inflammatory responses and enhance the survival rate of the septic mice. Mechanistically, pyroEV membrane-expressed ASC binds to B cells to repress cell death by repressing Toll-like receptor 4. This study uncovered the characteristics of pyroEVs and their therapeutic role in sepsis and B cell-mediated immune response.

Apoptosis releases hydrogen sulfide to inhibit Th17 cell differentiation.

Over 50 billion cells undergo apoptosis each day in an adult human to maintain immune homeostasis. Hydrogen sulfide (H2S) is also required to safeguard the function of immune response. However, it is unknown whether apoptosis regulates H2S production. Here, we show that apoptosis-deficient MRL/lpr (B6.MRL-Faslpr/J) and Bim-/- (B6.129S1-Bcl2l11tm1.1Ast/J) mice exhibit significantly reduced H2S levels along with aberrant differentiation of Th17 cells, which can be rescued by the additional H2S. Moreover, apoptotic cells and vesicles (apoVs) express key H2S-generating enzymes and generate a significant amount of H2S, indicating that apoptotic metabolism is an important source of H2S. Mechanistically, H2S sulfhydrates selenoprotein F (Sep15) to promote signal transducer and activator of transcription 1 (STAT1) phosphorylation and suppress STAT3 phosphorylation, leading to the inhibition of Th17 cell differentiation. Taken together, this study reveals a previously unknown role of apoptosis in maintaining H2S homeostasis and the unique role of H2S in regulating Th17 cell differentiation via sulfhydration of Sep15C38.

Extracellular vesicles and their indispensable roles in pathogenesis and treatment of inflammatory bowel disease: A comprehensive review.

Inflammatory bowel disease (IBD) is a global disease with rising incidence worldwide, and its debilitating symptoms and dissatisfactory therapies have brought heavy burdens for patients. Extracellular vesicles (EVs), a heterogeneous population of lipid bilayer membranes containing abundant bioactive molecules, have been indicated to play important roles in the pathogenesis and treatment of many diseases. However, to our knowledge, comprehensive reviews summarizing the various roles of diverse source-derived EVs in the pathogenesis and treatment of IBD are still lacking. This review, not only summarizes the EV characteristics, but also focuses on the multiple roles of diverse EVs in IBD pathogenesis and their treatment potential. In addition, hoping to push forward the research frontiers, we point out several challenges that the researchers are faced, about EVs in current IBD research and future therapeutic applications. We also put forward our prospects on future exploration regarding EVs in IBD treatment, including developing IBD vaccines and paying more attention on apoptotic vesicles. This review is aimed to enrich the knowledge on the indispensable roles of EVs in IBD pathogenesis and treatment, providing ideas and reference for future therapeutic strategy for IBD treatment.

Klotho enhances bone regenerative function of hPDLSCs via modulating immunoregulatory function and cell autophagy.

BACKGROUND: Human periodontal ligament stem cells (hPDLSCs) have a superior ability to promote the formation of new bones and achieve tissue regeneration. However, mesenchymal stem cells (MSCs) are placed in harsh environments after transplantation, and the hostile microenvironment reduces their stemness and hinders their therapeutic effects. Klotho is an antiaging protein that participates in the regulation of stress resistance. In our previous study, we demonstrated the protective ability of Klotho in hPDLSCs. METHODS: A cranial bone defect model of rats was constructed, and the hPDLSCs with or without Klotho pretreatment were transplanted into the defects. Histochemical staining and micro-computed tomography were used to detect cell survival, osteogenesis, and immunoregulatory effects of hPDLSCs after transplantation. The in vitro capacity of hPDLSCs was measured by a macrophage polarization test and the inflammatory level of macrophages. Furthermore, we explored autophagy activity in hPDLSCs, which may be affected by Klotho to regulate cell homeostasis. RESULTS: Pretreatment with the recombinant human Klotho protein improved cell survival after hPDLSC transplantation and enhanced their ability to promote bone regeneration. Furthermore, Klotho pretreatment can promote stem cell immunomodulatory effects in macrophages and modulate cell autophagy activity, in vivo and in vitro. CONCLUSION: These findings suggest that the Klotho protein protects hPDLSCs from stress after transplantation to maintain stem cell function via enhancing the immunomodulatory ability of hPDLSCs and inhibiting cell autophagy.

Immunomodulatory properties of mesenchymal stem cells/dental stem cells and their therapeutic applications.

Mesenchymal stem/stromal cells (MSCs) are widely distributed in the body and play essential roles in tissue regeneration and homeostasis. MSCs can be isolated from discarded tissues, expanded in vitro and used as therapeutics for autoimmune diseases and other chronic disorders. MSCs promote tissue regeneration and homeostasis by primarily acting on immune cells. At least six different types of MSCs have been isolated from postnatal dental tissues and have remarkable immunomodulatory properties. Dental stem cells (DSCs) have been demonstrated to have therapeutic effects on several systemic inflammatory diseases. Conversely, MSCs derived from nondental tissues such as the umbilical cord exhibit great benefits in the management of periodontitis in preclinical studies. Here, we discuss the main therapeutic uses of MSCs/DSCs, their mechanisms, extrinsic inflammatory cues and the intrinsic metabolic circuitries that govern the immunomodulatory functions of MSCs/DSCs. Increased understanding of the mechanisms underpinning the immunomodulatory functions of MSCs/DSCs is expected to aid in the development of more potent and precise MSC/DSC-based therapeutics.

Electrostatic Charge-Mediated Apoptotic Vesicle Biodistribution Attenuates Sepsis by Switching Neutrophil NETosis to Apoptosis.

Mesenchymal stem cell (MSC) therapy can attenuate organ damage and reduce mortality in sepsis; however, the detailed mechanism is not fully elucidated. In this study, it is shown that MSC-derived apoptotic vesicles (apoVs) can ameliorate multiple organ dysfunction and improve survival in septic mice. Mechanistically, it is found that tail vein-infused apoVs mainly accumulate in the bone marrow of septic mice via electrostatic charge interactions with positively charged neutrophil extracellular traps (NETs). Moreover, apoVs switch neutrophils NETosis to apoptosis via the apoV-Fas ligand (FasL)-activated Fas pathway. In summary, these findings uncover a previously unknown role of apoVs in sepsis treatment and an electrostatic charge-directed target therapeutic mechanism, suggesting that cell death is associated with disease development and therapy.

More natural more better: triple natural anti-oxidant puerarin/ferulic acid/polydopamine incorporated hydrogel for wound healing.

BACKGROUND: During wound healing, the overproduction of reactive oxygen species (ROS) can break the cellular oxidant/antioxidant balance, which prolongs healing. The wound dressings targeting the mitigation of ROS will be of great advantages for the wound healing. puerarin (PUE) and ferulic acid (FA) are natural compounds derived from herbs that exhibit multiple pharmacological activities, such as antioxidant and anti-inflammatory effects. Polydopamine (PDA) is made from natural dopamine and shows excellent antioxidant function. Therefore, the combination of natural antioxidants into hydrogel dressing is a promising therapy for wound healing. RESULTS: Hydrogel wound dressings have been developed by incorporating PUE or FA via PDA nanoparticles (NPs) into polyethylene glycol diacrylate (PEG-DA) hydrogel. This hydrogel can load natural antioxidant drugs and retain the drug in the gel network for a long period due to the presence of PDA NPs. Under oxidative stress, this hydrogel can improve the activity of superoxide dismutase and glutathione peroxidase and reduce the levels of ROS and malondialdehyde, thus preventing oxidative damage to cells, and then promoting wound healing, tissue regeneration, and collagen accumulation. CONCLUSION: Overall, this triple antioxidant hydrogel accelerates wound healing by alleviating oxidative injury. Our study thus provides a new way about co-delivery of multiple antioxidant natural molecules from herbs via antioxidant nanoparticles for wound healing and skin regeneration.

Downregulation of Linc-RNA activator of myogenesis lncRNA participates in FGF2-mediated proliferation of human periodontal ligament stem cells.

BACKGROUND: Accelerated proliferation of human periodontal ligament stem cells (PDLSCs) is present in periodontitis. It is known that fibroblast growth factor 2 (FGF2) regulates the proliferation of PDLSCs, while the function of FGF2 in myogenic cell differentiation is mediated by Linc-RNA Activator of Myogenesis (Linc-RAM) lncRNA. Therefore, Linc-RAM lncRNA may also participate in periodontitis. METHODS: This study included 28 patients with periodontitis (patient group) and 22 patients without periodontitis but received orthodontic treatment (control group) in the stomatological hospital of Sun Yat-Sen university. Gingival biopsies were obtained from participants. RT-qPCR, cell transfection, cell proliferation assay and western blot were carrying out to analyze the samples. RESULTS: We found that FGF2 mRNA was upregulated, while Linc-RAM was downregulated in PDLSCs derived from periodontitis-affected teeth than in healthy teeth. FGF2 mRNA and Linc-RAM were inversely correlated in both types of PDLSCs. FGF2 overexpression led to inhibited Linc-RAM expression in PDLSCs derived from periodontitis-affected teeth and promoted the proliferation of PDLSCs. Linc-RAM overexpression failed to significantly affect FGF2 expression but attenuated the enhancing effects of FGF2 overexpression on the proliferation of PDLSCs. CONCLUSIONS: Therefore, downregulation of Linc-RAM lncRNA may participate in FGF-2 mediated- proliferation of human PDLSCs.

Effect of polyvinylphosphonic acid on resin-dentin bonds and the cytotoxicity of mouse dental papilla cell-23.

STATEMENT OF PROBLEM: Polyvinylphosphonic acid (PVPA) could be used as a biomimetic remineralization analog and a matrix metalloproteinases (MMPs) inhibitor. However, studies are lacking regarding the performance of PVPA in dental bonding systems for maintaining the durability of the resin-dentin bond. PURPOSE: The purpose of this in vitro study was to investigate the effect of PVPA on the durability of resin-dentin bonds and the viability of mouse dental papilla cell-23 (MDPC-23). The mechanical properties of resin-dentin interfaces during long-term storage were analyzed, and the potential application of PVPA as a biomimetic remineralization analog in adhesive dentistry was evaluated. MATERIAL AND METHODS: Seventy-five extracted noncarious human third molars were collected and randomly divided into 5 groups, and then the microtensile bond strength (µTBS) data and scanning electron microscope (SEM) images were used to evaluate the preservation condition of resin-dentin bonds after 1 day, 6 months, and 1 year of storage. The cytotoxicity of PVPA was detected by cell proliferation assay and cell apoptosis assay. RESULTS: Compared with the control and chlorhexidine (CHX) groups, the combined group (treated with both 200-µg/mL PVPA and biomimetic remineralization) had excellent bond durability. The exposed collagen fibril from the PVPA-treated groups (included 200-µg/mL and 500-µg/mL PVPA groups and a combined group) still showed integrity after 1 year of storage when compared with the control group. PVPA up to 500 µg/mL showed no cytotoxicity to MDPC-23 and did not inhibit cell growth. CONCLUSIONS: This study offered evidence that PVPA did not result in cytotoxicity at low concentrations as an MMP inhibitor and a biomimetic remineralization analog. In addition, the application of PVPA improved bond strength and preserved collagen integrity after 1 year of in vitro storage.

Polydopamine/puerarin nanoparticle-incorporated hybrid hydrogels for enhanced wound healing.

Oxidative damage generated by various biochemical pathways can disrupt the oxidant/antioxidant balance in cells, causing slow wound healing and tissue regeneration; in this regard, a hydrogel dressing with antioxidant properties can promote wound healing; however, its design is still a challenge. Herein, a polydopamine/puerarin (PDA/PUE) nanoparticle-incorporated polyethylene glycol diacrylate hybrid hydrogel (PEG-DA/PDA/PUE) with antioxidant properties was prepared and used as a wound-healing material. Experimental observations indicated that the PEG-DA/PDA/PUE hydrogel possessed excellent swelling capacity and mechanical property. Moreover, the antioxidant capability was enhanced with an increase in the concentration of polydopamine/puerarin nanoparticles in the hydrogel. The hydrogel presented good cell proliferation and antioxidant activity, including a decrease in ROS and increase in the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity under oxidative stress conditions. Furthermore, the full-thickness skin-defect-regeneration process could be accelerated via the antioxidant hydrogel treatment. This study validated the potential applications of an antioxidant hydrogel for wound healing.

Short implants (5-8 mm) vs long implants (≥10 mm) with augmentation in atrophic posterior jaws: A meta-analysis of randomised controlled trials.

The aim of this systematic review was to compare the survival rate, marginal bone loss changes and complications between short implants (5-8 mm) and long implants (≥10 mm) with a bone-augmented procedure in the posterior jaw. An electronic search of the MEDLINE (PubMed), Embase and Cochrane Library databases through September 2018 was done to identify randomised controlled trials (RCT) assessing short implants and long implants with at least a 1-year follow-up period after loading. A quantitative meta-analysis was conducted on the survival rate, marginal bone loss changes and complications. Ten RCTs met the inclusion criteria. There were no significant differences in the survival rate (RR: 1.01; 95% CI: [0.99, 1.03]; P = .32) and complications (RR: 0.48; 95% CI: [0.20, 1.17]; P = .11) between the two groups. Compared with the long implant group, the short implant group had a lower marginal bone loss change, and the effect measure was significant (mean difference: -0.13; 95% CI: [-0.20, -0.06]; P < .05). This systematic review showed no difference between the survival rates and complications of short implants (5-8 mm) and long implants (≥10 mm). The marginal bone loss changes in short implants are lower than those in long implants.

Comparison Between a Computer-Aided Surgical Template and the Free-Hand Method: A Systematic Review and Meta-Analysis.

BACKGROUND: During implantation planning, dentists should be able to make an informed decision regarding whether to use an implant template to assist the surgery. PURPOSE: The aim of this meta-analysis was to assess the results of implantation with or without an implant template based on the accuracy, survival rate, and other considerations. MATERIALS AND METHODS: In January 2018, a systematic review was undertaken for randomized controlled trials and retrospective and prospective cohort studies with relevance to implant accuracy and the survival rate between the implant template and free-hand method. The odds ratios (ORs) of the survival rate and the mean difference of accuracy deviation from the selected papers were estimated by meta-analysis. RESULTS: Of the 362 screened articles, 6 studies were included in the meta-analysis. Comparison of the survival rate of implant surgery with or without an implant template revealed no significant result (OR = 1.71, 95% confidence interval [CI] 0.65-4.51). Significant differences in accuracy were observed in angular (mean difference = -5.45 degrees, 95% CI -0.66 to -4.24 degrees) and apical deviation (mean difference = -0.83 mm, 95% CI -1.12 to -0.54). CONCLUSIONS: With the technology of computer-aided surgical template, implant placement can be more accurate than free-hand operation. No significant difference is observed in the survival rate between template and free-hand.

Zein/gelatin/nanohydroxyapatite nanofibrous scaffolds are biocompatible and promote osteogenic differentiation of human periodontal ligament stem cells.

In bone tissue engineering, it is important for biomaterials to promote the osteogenic differentiation of stem cells to achieve tissue regeneration. Therefore, it is critical to develop biomaterials with excellent cytocompatibility and osteoinductive ability. In our previous study, we found a zein/gelatin electrospinning scaffold with good biocompatibility, but low osteoinductive ability for human periodontal ligament stem cells (hPDLSCs). Therefore, herein, we fabricated novel zein/gelatin/nanohydroxyapatite (zein/gelatin/nHAp) nanofibrous membranes to overcome the drawbacks of the zein/gelatin scaffold. The results showed that the surface wettability of the zein/gelatin/nHAp nanofiber membranes was increased. Moreover, the inclusion of nHAp facilitated the attachment, proliferation, and osteogenic differentiation of hPDLSCs. Overall, the zein/gelatin/nHAp nanofiber membranes showed good biocompatibility and osteoinductive activity for hPDLSCs in vitro and in vivo; this suggested potential applications of these membranes in bone tissue engineering.

Halloysite Nanotube Based Scaffold for Enhanced Bone Regeneration.

Bone regeneration remains a clinical challenge with limited bone substitutes, urging for effective alternative strategies. Nanotubes, especially carbon nanotubes and titanium dioxide nanotubes, have been widely utilized for bone regeneration; however, their further applications were limited by the composition and degradability. As naturally occurring aluminosilicate nanoclay, halloysite nanotubes (HNTs), with good biocompatibility, functionality, and nanotubular structures, may be a promising platform for promoting bone regeneration. Herein, we presented a HNTs incorporated hydrogel and explored the potential bone tissue engineering applications of HNTs. The HNTs encapsulated hydrogel was simply fabricated by using the photopolymerization method with gelatin methacrylate (GelMA) and HNTs. The incorporation of HNTs led to an enhanced mechanical performance while maintaining a good cytocompatibility in vitro. The osteogenic activities of the HNTs incorporated platform have also been studied in vitro and in vivo. Remarkably, the addition of HNTs obviously upregulated the expression of osteogenic differentiation-related genes and concomitant protein of human dental pulp stem cells (hDPSCs) and therefore facilitated subsequent bone regeneration in calvarial defects of rats. Overall, the results obtained in this study highlight the bone regeneration capacity of HNTs, which may enhance current understanding of HNTs, and present a promising alternative strategy for bone regeneration.

Effect of matrix metalloproteinase 8 inhibitor and chlorhexidine on the cytotoxicity, oxidative stress and cytokine level of MDPC-23.

OBJECTIVE: This study investigated the effect of matrix metalloproteinase-8 inhibitor I (MMP8-I) and chlorhexidine (CHX) on the viability, oxidative stress and cytokine secretion of MDPC-23 under short-term (30min) and long-term (3 days) culture. METHODS: MDPC-23 were treated with MMP8-I or CHX for 30min, 1day, 2days and 3days to detect the proliferation by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. In the following assays, MDPC-23 treated with 0.0003% CHX were referred to CHX group, treated with 8µM MMP8-I were MMP8-I group. Cells without additional treatment were regarded as control group. The cell cycle, reactive oxygen species (ROS) level, and apoptosis were assessed by flow cytometry. The cytokine level was quantified by enzyme-linked immunosorbent assay (ELISA). RESULTS: In 30min, CHX at concentrations higher than 0.0003% dilution inhibited cell proliferation when compared to the control group. MMP8-I (0.1-500µM) showed no obvious cytotoxicity to MDPC-23, and MMP8-I (1000µM) inhibited cell proliferation. In 3 days, CHX (0.0003%) significantly inhibited cell growth, while MMP8-I (8µM) had no cytotoxicity. In the CHX group, the S phase population was decreased, and cellular ROS were increased in 3 days. In the MMP8-I group, the change of S phase population and cellular ROS was not significant compared with the control group. Cell apoptosis was not elevated in the MMP8-I group, while the apoptosis rate was increased in the CHX group both in 30min and 3 days. In 30min, CHX treatment significantly increased the secretion of interleukin (IL)-1ß and IL-8, but slightly increased the secretion of IL-10, while MMP8-I caused no change in cytokines. In 3 days, CHX treatment significantly increased the secretion of IL-1ß, IL-6, and IL-8, and inhibited the secretion of IL-10. MMP8-I treatment caused the increase of IL-6. SIGNIFICANCE: Compared with CHX, MMP8-I at low concentration did not result in cytotoxicity, oxidative stress, or the disorder of immune response.

Effect of matrix metalloproteinase 8 inhibitor on resin-dentin bonds.

OBJECTIVES: This study investigated the effect of matrix metalloproteinase 8 (MMP-8) on resin-dentin bonds, assessed the mechanical properties of the interfaces over time, and discussed the potential application of MMP-8 inhibitor I (MMP8-I) as a specific MMP-8 inhibitor to be incorporated into dental adhesives. METHODS: The activation and inhibition of MMP-8 was detected by colorimetric assay. After 1 day, 6 months and 1 year of storage of Control, MMP8-I, and chlorhexidine (CHX) groups, the microtensile bond strengths (µTBS) were used to evaluate the bond strength and failure mode distributions, and nanoleakage analysis was used to evaluate the minor scattered silver particles. RESULTS: Colorimetric assay showed that the activated MMP-8 was enhanced by adhesive procedures, while it was inhibited by the additional treatment of MMP8-I or CHX. Compared with the Control and CHX groups, the MMP8-I group had significantly higher bond strength and the hybrid layer from the MMP8-I-treated dentin exhibited structural integrity of the collagen network and decreased silver nitrate penetration after 1 year of storage. SIGNIFICANCE: MMP-8 inhibition I protects against the degradation of resin-dentin bonds over time, which is better than broad-scale enzyme inhibitor CHX. It shows that MMP8-I may be used in dentistry for preventing collagen degradation within hybrid layers to extend the longevity of resin-dentin bonds.

Oestrogen retains human periodontal ligament stem cells stemness in long-term culture.

OBJECTIVES: During long-term culture, loss of stemness is observed which greatly restricts the application of human periodontal ligament stem cells (hPDLSCs) in tissue regeneration. Oestrogen (E2) was found to significantly enhance the proliferation and osteogenic differentiation capacity in mesenchymal stem cells. Therefore, in this study, we investigated effects of E2 on hPDLSCs stemness in long-term culture. MATERIALS AND METHODS: Effects of E2 on hPDLSCs stemness were systematically evaluated. To characterize underlying the mechanisms, its effects on PI3K/AKT signalling pathway were determined. RESULTS: Our results showed that E2 was able to enhance the proliferation, modify cell cycle, up-regulate stemness-related genes expression, promote osteogenic differentiation and elevate the positive rate of CD146 and STRO-1 over 10 passages in hPDLSCs. Importantly, PI3K/AKT signing pathway might play a role in these effects. CONCLUSIONS: These findings suggest that E2 retains hPDLSCs stemness in long-term culture, which might enhance its application in tissue engineering.

Poly(ester amide)-based hybrid hydrogels for efficient transdermal insulin delivery.

Transdermal drug delivery is an attractive, non-invasive treatment. It can avoid first-pass hepatic metabolism and provides the possibility of self-administration. Hydrogels are promising biomaterials due to their important qualities such as biocompatibility and biodegradability. Recently, there has been tremendous growth in the area of hydrogels for transdermal drug delivery. In this work, a new kind of arginine-based poly(ester amide) (Arg-PEA) and polyethylene glycol diacrylamide (PEG-DA) hybrid hydrogel was developed for transdermal drug delivery. The hydrogels not only possess excellent swelling capacity, but also have good mechanical properties, which were then evaluated as drug delivery agents using insulin as a model system. Cytotoxicity testing and in vivo skin irritation tests demonstrated that the hydrogels were biocompatible. Finally, the results indicated that the prepared hydrogels could not only perform transdermal drug delivery, but also might regulate blood glucose levels in a mouse model with streptozotocin-induced diabetes.

MicroRNA-214 Suppresses Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Targeting ATF4.

Periodontitis is the main cause of adult tooth loss. Stem cell-based tissue engineering has become a promising therapy for periodontitis treatment. To date, human periodontal ligament stem cells (hPDLSCs) have been shown to be a favorable source for tissue engineering, but modulatory mechanisms of hPDLSCs remain unclear. Approximately 60% of mammalian genes are the targets of over 2000 miRNAs in multiple human cell types, and miRNAs are able to influence various biological processes in the human body, including bone formation. In this study, we found that after osteogenic induction, miR-214 was significantly decreased in hPDLSCs; therefore, we examined the effects of miR-214 on osteogenic differentiation. Computational miRNA target prediction analyses and luciferase reporter assays revealed that activating transcription factor 4 (ATF4) is a direct target of miR-214. We prepared cells overexpressing miR-214 and found that miR-214 negatively regulates osteogenic differentiation of hPDLSCs. For the target of miR-214, ATF4 protein expression level was decreased after induction. In conclusion, we found that miR-214-ATF4 axis is a novel pathway for regulating hPDLSC osteogenic differentiation.

Effects of Intermittent Administration of Parathyroid Hormone (1-34) on Bone Differentiation in Stromal Precursor Antigen-1 Positive Human Periodontal Ligament Stem Cells.

Periodontitis is the most common cause of tooth loss and bone destruction in adults worldwide. Human periodontal ligament stem cells (hPDLSCs) may represent promising new therapeutic biomaterials for tissue engineering applications. Stromal precursor antigen-1 (STRO-1) has been shown to have roles in adherence, proliferation, and multipotency. Parathyroid hormone (PTH) has been shown to enhance proliferation in osteoblasts. Therefore, in this study, we aimed to compare the functions of STRO-1(+) and STRO-1(-) hPDLSCs and to investigate the effects of PTH on the osteogenic capacity of STRO-1(+) hPDLSCs in order to evaluate their potential applications in the treatment of periodontitis. Our data showed that STRO-1(+) hPDLSCs expressed higher levels of the PTH-1 receptor (PTH1R) than STRO-1(-) hPDLSCs. In addition, intermittent PTH treatment enhanced the expression of PTH1R and osteogenesis-related genes in STRO-1(+) hPDLSCs. PTH-treated cells also exhibited increased alkaline phosphatase activity and mineralization ability. Therefore, STRO-1(+) hPDLSCs represented a more promising cell resource for biomaterials and tissue engineering applications. Intermittent PTH treatment improved the capacity for STRO-1(+) hPDLSCs to repair damaged tissue and ameliorate the symptoms of periodontitis.