MicroRNA-224 enhances the osteoblastic differentiation of hMSCs via Rac1.

Osteogenesis is the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. MicroRNAs (miRNAs) are short noncoding RNAs that target specific genes to mediate translational activities. In this study, we investigated how miR-224 regulates the osteoblastic differentiation of human MSCs (hMSCs) as well as the underlying mechanism. The results revealed the upregulation of miR-224 during hMSC differentiation. In vitro experiments showed that the downregulation of miR-224 suppressed the differentiation of hMSCs into osteoblasts. However, upregulation of miR-224 was concomitant with increased expression of relevant genes and augmented activity of alkaline phosphatase. Furthermore, the results indicated that Rac1 acted as the bona fide target of miR-224 and that Rac1 depletion promoted osteogenic differentiation in miR-224-silenced hMSCs. In addition, we found that both JAK/STAT3 and Wnt/ß-catenin pathways were repressed by Rac1 depletion using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and immunofluorescence. Our data indicate a novel molecular mechanism in relation to hMSCs differentiation into osteoblasts, which may facilitate bone anabolism via miR-224. SIGNIFICANCE OF THE STUDY: In this study, we mainly explored the effects of miR-224 on hMSCs differentiation into osteoblasts. We find that induced miR-224 expression in hMSCs is considered closely associated with specific osteogenesis-related genes, alkaline phosphatase activity, and matrix mineralization, indicating that miR-224 may serve as a promising biomarker for osteogenic differentiation. Our data indicate a novel molecular mechanism in relation to hMSCs differentiation into osteoblasts, which may facilitate bone anabolism via miR-224.

The Role of Caspase-11 and Pyroptosis in the Regulation of Inflammation in Peri-Implantitis.

Peri-implantitis is an important cause of oral implant failure. In the past, TLR4 and TLR2 in the Toll-like family were generally considered as the key immune recognition receptors regulating peri-implantitis. However, under the guidance of this theory, there are still some unexplainable peri-implantitis symptoms. With the discovery of novel intracellular LPS receptor Caspase-11, a new understanding of inflammatory signaling and immune regulation in the development of peri-implantitis has been gained. However, the regulatory role of Caspase-11 in peri-implantitis and its crosstalk with the TLR4 pathway remain unclear. The therapeutic effect of drugs targeting Caspase-11 on peri-implantitis is still in its early stages. In view of this situation, this paper reviews the possible role of Caspase-11 in peri-implant inflammation, elaborated the entry process of LPS and the activation mechanism of Caspase-11, and analyzes the differences in Caspase-11 between commonly studied animals, mice and humans. The current research hotspots and challenges are also analyzed to provide new insights and ideas for researchers.

Caspase-11/4 is involved in bacteria-mediated periodontitis by promoting the release of interleukin-1 ß and tumor necrosis factor-α.

OBJECTIVE: This study investigated the main mechanism and role of caspase-11/4 as a pattern recognition receptor (PRR) in periodontitis through caspase-11 inhibition. DESIGN: Clinical tissue samples were collected from patients with periodontitis and healthy volunteers and evaluated through hematoxylin-eosin (HE) staining, immunohistochemical (IHC) staining, and real-time quantitative PCR (RT-qPCR). In the rat periodontitis model, both these staining procedures, RT-qPCR, and western blotting were used to evaluate the histological, mRNA, and protein levels of caspase-11, interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). In vitro, the role of caspase-11, inhibited by siRNA, was investigated by analyzing the mRNA and protein levels of IL-1ß and TNF-α in Porphylinomonas gingivalis (P. gingivalis) lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. RESULTS: Histological and molecular biological results of clinical and experimental animal periodontitis samples indicated that caspase-11/4 mRNA and protein levels significantly increased in inflammatory tissues. Caspase-11 is mainly distributed in leukocytes, which are labeled by CD45 in the submucosa. In vitro results further confirmed that the expression of caspase-11/4, IL-1ß, and TNF-α significantly increased in LPS-stimulated macrophages, and these changes were significantly attenuated by inhibiting caspase-11/4 expression. CONCLUSIONS: The function of caspase-11 in rat periodontitis models is similar to that of caspase-4 in human clinical periodontitis. IL-1ß and TNF-α release in periodontitis depends on the recognition of P. gingivalis LPS by caspase-11/4.

Precise Diagnosis and Therapy of Bone Cancer Using Near-Infrared Lights.

Bone is a preferred site for both primary and metastasis tumors. Current diagnosis of osteopathia typically relies on noninvasive skeleton radiography technology. However, due to the limited resolution of ionizing radiation, accurate diagnosis and effective identification impairment areas are still lacking. Near-infrared (NIR) bioimaging, especially in the NIR-II (1000-1700 nm) regions, can provide high sensitivity and spatiotemporal resolution bioimaging compared to the conventional radiography. Thus, NIR bioimaging affords intraoperative visualization and imaging-guided surgery, aiming to overcome challenges associated with theranostics of osteopathia and bone tumors. The present review aimed to summarize the latest evidence on the use of NIR probes for the targeting bone imaging. We further highlight the recent advances in bone photoX (X presents thermal, dynamic, and immuno) therapy through NIR probes, in particular combination with other customized therapeutic agents could provide high-efficiency treatment for bone tumors.

Long non-coding RNAs mortal obligate RNA transcript regulates the proliferation of human periodontal ligament stem cells and affects the recurrence of periodontitis.

OBJECTIVE: The aim of this study is to investigate the role of long non-coding RNAs (lncRNA), mortal obligate RNA transcript (MORT), in human periodontal ligament stem cells. DESIGN: Periodontal ligament tissues were collected from 48 periodontitis patients underwent tooth extraction and 38 people in similar age and gender distributions who experienced orthodontic treatment. After treatment, periodontitis patients were followed up for 2 years. MORT in periodontal ligament stem cells (PDLSCs) was detected by qRT-PCR. Proliferation of PDLSCs was detected by CCK-8 assay. RESULTS: The proliferation rate of PDLSCs isolated from periodontitis-affected teeth was significantly higher than PDLSCs from healthy teeth. Overexpression of MORT inhibited the proliferation of both types of periodontal ligament stem cells. After treatment, periodontitis patients were followed up for 2 years and patients with high level of MORT expression showed relatively lower recurrence rate comparing to low expression group. CONCLUSION: MORT is involved in the proliferation of human PDLSCs and affects the recurrence of periodontitis.