Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells.

BACKGROUND: The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years, which also may lead to some complications such as alveolar bone resorption or tooth root resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing. It is also reported that LIPUS could reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear. AIM: To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms. METHODS: A rat model of OTM was established, and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction, Western blot, alkaline phosphatase (ALP) staining, and Alizarin red staining. The expression of Yes-associated protein (YAP1), the actin cytoskeleton, and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA (siRNA) application via immunofluorescence. RESULTS: The force treatment inhibited the osteogenic differentiation potential of hBMSCs; moreover, the expression of osteogenesis markers, such as type 1 collagen (COL1), runt-related transcription factor 2, ALP, and osteocalcin (OCN), decreased. LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force. Mechanically, the expression of LaminA/C, F-actin, and YAP1 was downregulated after force treatment, which could be rescued by LIPUS. Moreover, the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment. Consistently, LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo. The decreased expression of COL1, OCN, and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS. CONCLUSION: LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis, which may be a promising strategy to reduce the orthodontic treatment process.

Stem Cells from Human Exfoliated Deciduous Teeth Alleviate High-Altitude Cerebral Oedema by Shifting Microglial M1/M2 Polarisation.

OBJECTIVE: To explore the high-efficiency and low-risk prevention and treatment strategies for stem cells from human exfoliated deciduous teeth (SHED) for high-altitude cerebral oedema. METHODS: A low-pressure and low-oxygen tank mimicking high-altitude conditions was used to establish the high-altitude cerebral oedema animal model. The preventive effects of SHED for cerebral oedema were then evaluated by haematoxylin and eosin (H&E) and histological staining. In vitro, SHED was co-cultured with BV-2 to analyse the effects of SHED by western blot and immunofluorescence staining. RESULTS: SHED can prevent and treat cerebral oedema in a high altitude rat animal model. Mechanistically, SHED treatment can protect brain cells from apoptosis induced by high altitude condition. Moreover, SHED treatment can inhibit M1-type polarisation and promote M2-type polarisation of microglia cells via the suppression of hypoxia inducible factor (HIF)- 1α-mediated extracellular signal-regulated kinase (ERK) signalling activated in high altitude condition. CONCLUSION: SHED treatment can relieve high-altitude cerebral oedema via inhibiting HIF- 1α-mediated ERK signalling, which indicates that SHED is a promising alternative strategy to prevent and treat high-altitude cerebral oedema.

Mechanical force-promoted osteoclastic differentiation via periodontal ligament stem cell exosomal protein ANXA3.

Exosomes play a critical role in intracellular communication. The biogenesis and function of exosomes are regulated by multiple biochemical factors. In the present study, we find that mechanical force promotes the biogenesis of exosomes derived from periodontal ligament stem cells (PDLSCs) and alters the exosomal proteome profile to induce osteoclastic differentiation. Mechanistically, mechanical force increases the level of exosomal proteins, especially annexin A3 (ANXA3), which facilitates exosome internalization to activate extracellular signal-regulated kinase (ERK), thus inducing osteoclast differentiation. Moreover, the infusion of exosomes derived from PDLSCs into mice promotes mechanical force-induced tooth movement and increases osteoclasts in the periodontal ligament. Collectively, this study demonstrates that mechanical force treatment promotes the biogenesis of exosomes from PDLSCs and increases exosomal protein ANXA3 to facilitate exosome internalization, which activates ERK phosphorylation, thus inducing osteoclast differentiation. Our findings shed light on new mechanisms for how mechanical force regulates the biology of exosomes and bone metabolism.

Stem Cells From Human Exfoliated Deciduous Teeth Alleviate Liver Cirrhosis via Inhibition of Gasdermin D-Executed Hepatocyte Pyroptosis.

Liver cirrhosis represents a type of end-stage liver disease with few effective therapies, which was characterized by damaged functional liver tissue due to long-term inflammation. Gasdermin D (GSDMD)-executed programmed necrosis is reported to be involved in inflammation. However, the role of GSDMD in liver cirrhosis remains unclear. In this study, we used a CCl4-induced cirrhosis model and found stem cells from human exfoliated deciduous teeth (SHED) infusion showed profound therapeutic effects for liver cirrhosis. Mechanistically, NLRP3 inflammasome-activated GSDMD and its pyroptosis were upregulated in liver cirrhosis, while SHED infusion could suppress the expression of GSDMD and Caspase-1, resulting in reduced hepatocyte pyroptosis and inflammatory cytokine IL-1ß release. Consistently, SHED could inhibit the elevated expression of NLRP3, GSDMD and Caspase-1 induced by CCl4 treatment in vitro co-culture system, which was mediated by decreasing reactive oxygen species (ROS) generation. Moreover, the pyroptosis inhibitor disulfiram showed similar therapeutic effects for liver cirrhosis as SHED. In conclusion, SHED alleviates CCl4-induced liver cirrhosis via inhibition of hepatocytes pyroptosis. Our findings could provide a potential treatment strategy and novel target for liver cirrhosis.

Aneurysmal bone cysts of the jaws: analysis of 17 cases.

PURPOSE: Aneurysmal bone cysts (ABCs) are benign osteolytic lesions that occur relatively rarely in the jaws. The aim of the present study was to investigate the clinical and radiographic characteristics, pathologic features, and treatment results of ABCs of the jaws (JABCs). MATERIALS AND METHODS: A retrospective analysis of a 20-year database, including 17 cases of JABC, was performed. RESULTS: A total of 17 patients, 9 males and 8 females, aged 7 to 47 years (mean 20.4, median 14), were included. Of the 17 lesions, 15 (88.2%) were located in the mandible and 2 (11.8%) in the maxilla. A painless (12 of 17, 70.6%) or painful (3 of 17, 17.6%) swelling was the most common clinical finding. The pathologic analyses revealed that 13 JABCs (76.5%) were secondary in nature, including 11 cases associated with ossifying fibroma. Radiologically, the lesions frequently presented as multilocular (58.8%), well-defined (70.6%) radiolucencies (82.4%). Two lesions (11.8%) recurred. CONCLUSIONS: Our results suggest that most JABCs are secondary in nature and frequently associated with ossifying fibroma. The patients with JABCs presented with various clinical and radiographic features and therefore often posed a diagnostic dilemma. Resection is the preferred treatment of JABCs.

Stem cells from human exfoliated deciduous teeth ameliorate concanavalin A-induced autoimmune hepatitis by protecting hepatocytes from apoptosis.

BACKGROUND: Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide, which emphasizes the urgent need to identify novel treatments. Stem cells from human exfoliated deciduous teeth (SHED), which are easy to obtain in a non-invasive manner, show pronounced proliferative and immunomodulatory capacities. AIM: To investigate the protective effects of SHED on concanavalin A (ConA)-induced hepatitis in mice, and to elucidate the associated regulatory mechanisms. METHODS: We used a ConA-induced acute hepatitis mouse model and an in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis, as well as the associated underlying mechanisms. RESULTS: SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3+, CD4+, tumor necrosis-alpha+, and interferon-gamma+ inflammatory cells. Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice. SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations. Mechanistically, ConA upregulated tumor necrosis-alpha and interferon-gamma expression, which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis, resulting in acute liver injury. SHED administration protected hepatocytes from ConA-induced apoptosis. CONCLUSION: SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway. Our findings could provide a potential treatment strategy for hepatitis.

Local Administration of Stem Cells from Human Exfoliated Primary Teeth Attenuate Experimental Periodontitis in Mice.

OBJECTIVE: To evaluate the therapeutic effect of local injection of stem cells from human exfoliated primary teeth (SHED) on periodontitis in mice. METHODS: Fifteen female mice were randomly divided into three groups: normal control group, periodontitis group and SHED treatment group. A periodontitis model was established by ligating a 0.2 mm orthodontic ligation wire to the maxillary first molar. The SHED group was injected with SHED at 3 weeks post-ligation. All mice were sacrificed and their maxillae were dissected five weeks post-ligation. Clinical assessments, micro-computed tomography (micro-CT) scanning, and histologic examination were used to evaluate the outcome of tissue regeneration. RESULTS: Micro-CT analysis showed that SHED administration significantly increased periodontal regeneration and decreased the distance between the cemento-enamel junction and the alveolar bone crest. In addition, histopathological photomicrographs showed new regenerated bone, the number of TNF-α-positive, IFN-γ-positive and CD4+ cells decreased, and osteoclasts-positive decreased in the periodontal defect area in the SHED group compared with the periodontitis group. CONCLUSION: SHED administration suppresses the expression of inflammatory factors, inhibits the production of osteoclasts, and promotes the regeneration of periodontal tissues.

Influence of Surface Chemistry on Adhesion and Osteo/Odontogenic Differentiation of Dental Pulp Stem Cells.

The complex interaction between extracellular matrix and cells makes the design of materials for dental regeneration challenging. Chemical composition is an important characteristic of biomaterial surfaces, which plays an essential role in modulating the adhesion and function of cells. The effect of different chemical groups on directing the fate of human dental pulp stem cells (hDPSCs) was thus explored in our study. A range of self-assembled monolayers (SAMs) with amino (-NH2), hydroxyl (-OH), carboxyl (-COOH), and methyl (-CH3) modifications were prepared. Proliferation, morphology, adhesion, and differentiation of hDPSCs were then analyzed to demonstrate the effects of surface chemical groups. The results showed that hDPSCs attached to the -NH2 surface displayed a highly branched osteocyte-like morphology with improved cell adhesion and proliferation abilities. Moreover, hDPSCs cultured on the -NH2 surface also tended to obtain an increased osteo/odontogenesis differentiation potential. However, the hDPSCs on the -COOH, -OH, and -CH3 surfaces preferred to maintain the mesenchymal stem cell-like phenotype. In summary, this study indicated the influence of chemical groups on hDPSCs in vitro and demonstrated that -NH2 might be a promising surface modification strategy to achieve improved biocompatibility, osteoconductivity/osteoinductivity, and osseointegration of dental implants, potentially facilitating dental tissue regeneration.