Proangiogenic effect and underlying mechanism of holmium oxide nanoparticles: a new biomaterial for tissue engineering.

BACKGROUND: Early angiogenesis provides nutrient supply for bone tissue repair, and insufficient angiogenesis will lead tissue engineering failure. Lanthanide metal nanoparticles (LM NPs) are the preferred materials for tissue engineering and can effectively promote angiogenesis. Holmium oxide nanoparticles (HNPs) are LM NPs with the function of bone tissue "tracking" labelling. Preliminary studies have shown that HNPs has potential of promote angiogenesis, but the specific role and mechanism remain unclear. This limits the biological application of HNPs. RESULTS: In this study, we confirmed that HNPs promoted early vessel formation, especially that of H-type vessels in vivo, thereby accelerating bone tissue repair. Moreover, HNPs promoted angiogenesis by increasing cell migration, which was mediated by filopodia extension in vitro. At the molecular level, HNPs interact with the membrane protein EphrinB2 in human umbilical vein endothelial cells (HUVECs), and phosphorylated EphrinB2 can bind and activate VAV2, which is an activator of the filopodia regulatory protein CDC42. When these three molecules were inhibited separately, angiogenesis was reduced. CONCLUSION: Overall, our study confirmed that HNPs increased cell migration to promote angiogenesis for the first time, which is beneficial for bone repair. The EphrinB2/VAV2/CDC42 signalling pathway regulates cell migration, which is an important target of angiogenesis. Thus, HNPs are a new candidate biomaterial for tissue engineering, providing new insights into their biological application.

Promotion effect of apical tooth germ cell-conditioned medium on osteoblastic differentiation of periodontal ligament stem cells through regulating miR-146a-5p.

BACKGROUND: MicroRNAs (miRNAs) play an important role in gene regulation that controls stem cells differentiation. Periodontal ligament stem cells (PDLSCs) could differentiate into osteo-/cementoblast-like cells that secretes cementum-like matrix both in vitro and in vivo. Whether miRNAs play key roles in osteoblastic differentiation of PDLSCs triggered by a special microenviroment remains elusive. In this study, we aimed to investigate potential miRNA expression changes in osteoblastic differentiation of PDLSCs by the induction of apical tooth germ cell-conditioned medium (APTG-CM). METHODS AND RESULTS: First, we analyzed the ability of APTG-CM to osteogenically differentiate PDLSCs. The results exhibited an enhanced mineralization ability, higher ALP activity and increased expression of osteogenic genes in APTG-CM-induced PDLSCs. Second, we used miRNA sequencing to analyze the miRNA expression profile of PDLSCs derived from three donors under 21-day induction or non-induction of APTG-CM. MiR-146a-5p was found to be up-regulated miRNA in induced PDLSCs and validated by RT-qPCR. Third, we used lentivirus-up/down system to verify the role of miR-146a-5p in the regulation of osteoblastic differentiation of PDLSCs. CONCLUSIONS: In conclusion, our results demonstrated that miR-146a-5p was involved in the promotion effect of APTG-CM on osteoblastic differentiation of PDLSCs, and suggested that miR-146a-5p might be a novel way in deciding the direction of PDLSCs differentiation.

Abnormal expression of long noncoding RNA FGD5-AS1 affects the development of periodontitis through regulating miR-142-3p/SOCS6/NF-κB pathway.

Periodontitis refers to the inflammation of gums and the surrounding structures and caused by a bacterial infection. The infection occurs owing to poor oral hygiene and could destroy the bone and the gum over time if left untreated. The present study identified the involvement of a key long noncoding RNA (lncRNA), i.e. FGD5-AS1, in the pathogenesis of periodontitis by assessing its expression in the gingival tissues of patients diagnosed with chronic periodontitis (CP). Overexpression of FGD5-AS1 in primary human periodontal ligament cells (PDLCs) significantly reduced the lipopolysaccharide (LPS)-induced periodontitis, whereas its suppression aggravated this injury. Moreover, the miR-142-3p was markedly expressed in the gingival samples of patients diagnosed with CP and LPS-induced PDLCs. We found that the FGD5-AS1-mediated reduction in the inflammation was mediated through downside regulation of miR-142-3p, as evident from the upregulation of SOCS6, a target gene of miR-142-3p. Furthermore, the association between FGD5-AS1 and NF-κB pathway was detected. FGD5-AS1 was found to protect against LPS-stimulated PDLC injury through restraining the NF-κB signals. Based on these findings, we conclude that up-regulation of lncRNA FGD5-AS1 could protect against periodontitis via regulating the miR-142-3p/SOCS6/NF-κB signals. Therefore, the FGD5-AS1/miR-142-3p/SOCS6 axis may act as an important indicator in explaining the pathogenesis of periodontitis.

Orthodontic management of inverted and impacted bilateral maxillary central incisors: a case report.

Complete inversion and impaction of both permanent central incisors is uncommon and rarely reported in the literature. In this report, we describe the treatment of maxillary central incisors that were completely inverted and impacted and positioned high in the vestibule. The esthetic results achieved provide an alternative to extraction or surgical repositioning.