Aim To investigate the in vitro biological effects of a nanoparticle bioceramic material, iRoot Fast Set root repair material (iRoot FS), on the proliferation, migration and osteo/odontogenic differentiation of human stem cells from the apical papilla (hSCAP), and to further explore the mechanism involved in osteo/odontogenic induction of iRoot FS. Methodology hSCAP were isolated and characterized in vitro. iRoot FS conditioned medium were prepared and used to treat hSCAP, while using mineral trioxide aggregate (MTA) conditioned medium as the positive control and regular medium as the negative control. MTT assay and BrdU labelling assay were performed to determine cell proliferation. Wound healing assay and transwell assay were conducted to evaluate cell migration. The osteo/odontogenic differentiation of hSCAP was evaluated by qPCR, Western blot and Alizarin red S staining. Wnt inhibitor was used for downregulating the expression level of β‐catenin of hSCAP. Results The cell proliferation of hSACP in the iRoot FS group was not significantly different compared with the control groups. The cell migration of hSCAP in the iRoot FS group was significantly increased than the MTA and negative control groups (P < 0.01). The expression levels of osteo/odontogenic markers and mineralization nodule formation of hSCAP in the iRoot FS group were significantly elevated (P < 0.01). Furthermore, iRoot FS enhanced the osteo/odontogenic differentiation of hSCAP by activating Wnt/β‐catenin signalling. Conclusions iRoot FS promoted the cell migration of hSCAP and enhanced their oseto/odontogenesis potential via the Wnt/β‐catenin pathway without cytotoxicity. iRoot FS had satisfactory biological properties and has potential to be used as an apical barrier in apexification or as a coronal sealing material in regenerative endodontic treatment.
iRoot FM exhibited excellent antibacterial activity against P. endodontalis and could improve the proliferation and differentiation of SCAP. The findings provide evidence that iRoot FM has potential as an intracanal medicament for endodontic procedures in immature permanent teeth.
This study aims to assess the risk factors of cardiovascular disease (CVD) and to determine the association of traditional and biologic disease-modifying anti-rheumatic drugs (DMARDs) with risk for CVD in Chinese rheumatoid arthritis (RA) patients. A cross-sectional cohort of 2013 RA patients from 21 hospitals around China was established. Medical history of CVD was documented. The patients' social background, clinical manifestations, comorbidities, and medications were also collected. Of the 2013 patients, 256 had CVD with an incidence of 12.7%. Compared with non-CVD controls, RA patients with CVD had a significantly advanced age, long-standing median disease duration, more often male and more deformity joints. Patients with CVD also had higher rates of smoking, rheumatoid nodules, interstitial lung disease, and anemia. The prevalence of comorbidities, including hypothyroidism, diabetes mellitus (DM), hypertension, and hyperlipidemia, was also significant higher in the CVD group. In contrast, patients treated with methotrexate, hydroxychloroquine (HCQ), and TNF blockers had lower incidence of CVD. The multivariate analysis showed that the use of HCQ was a protective factor of CVD, while hypertension, hyperlipidemia, and interstitial lung disease were independent risk factors of CVD. Our study shows that the independent risk factors of CVD include hypertension, hyperlipidemia, and interstitial lung disease. HCQ reduces the risk of CVD in patients with RA.
Aim To evaluate the effects of exosomes derived from stem cells from the apical papilla (SCAP‐Exos) in rats with experimentally induced pulpitis and the effects of SCAP‐Exos on the conversion of regulatory T cells (Tregs) and methylation status of the Foxp3 locus in Tregs in vitro. Methodology SCAP‐Exos were isolated and identified using transmission electron microscopy, western blotting, and nanoparticle tracking analysis. Lipopolysaccharide was used to experimentally induced pulpitis in rats, and the effects of SCAP‐Exos on the rats with pulpitis were detected using haematoxylin‐eosin staining and immunofluorescence staining. CD4+CD25‐ T cells were treated with different doses of SCAP‐Exos, and flow cytometric analysis was used to assess the effects of SCAP‐Exos on Treg proliferation and conversion. An enzyme‐linked immunosorbent assay (ELISA) was used to evaluate the expression of interleukin 10 (IL‐10). MethylTarget® technology was used to measure the methylation level of the Foxp3 locus in T cells. The expression levels of ten‐eleven‐translocation (Tet) 1, Tet2, and Tet3 in T cells were detected by real‐time PCR and western blotting. Results SCAP‐Exos had an elliptical vesicle‐like structure with a diameter of approximately 143.7 nm and expressed the exosomal markers Alix and CD9. SCAP‐Exo administration increased Treg accumulation in the inflamed dental pulp and alleviated inflammation in the dental pulp in vivo. SCAP‐Exos promoted Treg conversion in vitro. Mechanistically, SCAP‐Exos promoted Tet2‐mediated Foxp3 demethylation to maintain the stable expression of Foxp3. Conclusions SCAP‐Exos promoted Treg conversion and effectively alleviated inflammation in the dental pulp of rats. This study shows that SCAP‐Exos can regulate the local immune microenvironment to favour tissue regeneration, thus providing a potential novel strategy utilising SCAP‐Exos as a cell‐free approach to treat early inflammation of dental pulp in immature permanent teeth in the clinic.
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