Periosteum Containing Implicit Stem Cells: A Progressive Source of Inspiration for Bone Tissue Regeneration.

The periosteum is known as the thin connective tissue covering most bone surfaces. Its extrusive bone regeneration capacity was confirmed from the very first century-old studies. Recently, pluripotent stem cells in the periosteum with unique physiological properties were unveiled. Existing in dynamic contexts and regulated by complex molecular networks, periosteal stem cells emerge as having strong capabilities of proliferation and multipotential differentiation. Through continuous exploration of studies, we are now starting to acquire more insight into the great potential of the periosteum in bone formation and repair in situ or ectopically. It is undeniable that the periosteum is developing further into a more promising strategy to be harnessed in bone tissue regeneration. Here, we summarized the development and structure of the periosteum, cell markers, and the biological features of periosteal stem cells. Then, we reviewed their pivotal role in bone repair and the underlying molecular regulation. The understanding of periosteum-related cellular and molecular content will help enhance future research efforts and application transformation of the periosteum.

Porphyromonas gingivalis triggers inflammation in hepatocyte depend on ferroptosis via activating the NF-κB signaling pathway.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive fat deposition in hepatocytes caused by non-alcoholic liver injury. Porphyromonas gingivalis (P.g) is the main pathogen causing periodontitis, which can aggravate the progression of NAFLD in our previously study. The objective of this study was to further investigate the pathogenesis and moleculer michanisma of NAFLD aggravated by P.g. METHODS: A mouse model of NAFLD was established, and the changes of inflammatory factors and NF-κB signaling pathway in liver tissue and L-02 cells were analyzed by transcriptome sequencing, Western blot, IHC and RT-PCR. In addition, the NF-κB signaling pathway inhibitor QNZ and ferroptosis inhibitor Fer-1 were used to analyze the relationship between NF-κB signaling pathway and ferroptosis in vitro. RESULTS: In vivo and in vitro experiments, P.g can induce liver inflammation and activate NF-κB signaling pathway. At the same time, P.g promotes ferroptosis and inflammation in L-02 in vitro. QNZ alleviates ferroptosis and inflammatory activation in L-02. Fer-1 can relieve the L-02 inflammation caused by P.g products. CONCLUSION: Porphyromonas gingivalis can induce ferroptosis and inflammation in hepatocytes and further worsen liver lesions. The mechanism of ferroptosis in hepatocytes depends on NF-κB signaling pathway, which provides a new strategy for clinical treatment and prevention of NAFLD.

Effect of Aging on Tendon Biology, Biomechanics and Implications for Treatment Approaches.

Tendon aging is associated with an increasing prevalence of tendon injuries and/or chronic tendon diseases, such as tendinopathy, which affects approximately 25% of the adult population. Aged tendons are often characterized by a reduction in the number and functionality of tendon stem/progenitor cells (TSPCs), fragmented or disorganized collagen bundles, and an increased deposition of glycosaminoglycans (GAGs), leading to pain, inflammation, and impaired mobility. Although the exact pathology is unknown, overuse and microtrauma from aging are thought to be major causative factors. Due to the hypovascular and hypocellular nature of the tendon microenvironment, healing of aged tendons and related injuries is difficult using current pain/inflammation and surgical management techniques. Therefore, there is a need for novel therapies, specifically cellular therapy such as cell rejuvenation, due to the decreased regenerative capacity during aging. To augment the therapeutic strategies for treating tendon-aging-associated diseases and injuries, a comprehensive understanding of tendon aging pathology is needed. This review summarizes age-related tendon changes, including cell behaviors, extracellular matrix (ECM) composition, biomechanical properties and healing capacity. Additionally, the impact of conventional treatments (diet, exercise, and surgery) is discussed, and recent advanced strategies (cell rejuvenation) are highlighted to address aged tendon healing. This review underscores the molecular and cellular linkages between aged tendon biomechanical properties and the healing response, and provides an overview of current and novel strategies for treating aged tendons. Understanding the underlying rationale for future basic and translational studies of tendon aging is crucial to the development of advanced therapeutics for tendon regeneration.

Knockout of NRAGE promotes autophagy-related gene expression and the periodontitis process in mice.

BACKGROUND AND OBJECTIVE: Neurotrophin receptor-interacting MAGE homologue (NRAGE) plays a crucial role in the regulation of bone metabolism. The present study investigated the regulation role of NRAGE on autophagy activation and periodontitis process during experimental periodontitis. MATERIALS AND METHODS: Six-week-old wild-type (WT) and NRAGE-/- mice were randomly divided into three time points in the periodontitis groups (0, 2, and 4 weeks). Histopathological changes were determined using the tooth mobility, hematoxylin and eosin (H&E) staining, and micro-computed tomography (micro-CT). Osteoclasts activation and number were investigated using tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry, and real-time quantitative PCR (RT-PCR). The level of autophagy-related gene expression was measured using immunohistochemistry, immunofluorescence, and RT-PCR. RESULTS: H&E staining and Micro-CT showed that the destruction of the alveolar bone was considerably more severe in the NRAGE-/- group than the WT group after ligation. Tooth mobility in the NRAGE-/- group was obviously higher than that in the WT group. The activation and number of osteoclasts and the level of autophagy-related gene expression in NRAGE-/- group were significantly higher than that in WT group. CONCLUSIONS: The present study showed that knockout of NRAGE induced autophagy-related gene expression and accelerated the process of periodontitis disease via increasing the activity and differentiation of osteoclast.

Cellular Internalization-Induced Aggregation of Porous Silicon Nanoparticles for Ultrasound Imaging and Protein-Mediated Protection of Stem Cells.

Nanotechnology employs multifunctional engineered materials in the nanoscale range that provides many opportunities for translational stem cell research and therapy. Here, a cell-penetrating peptide (virus-1 transactivator of transcription)-conjugated, porous silicon nanoparticle (TPSi NP) loaded with the Wnt3a protein to increase both the cell survival rate and the delivery precision of stem cell transplantation via a combinational theranostic strategy is presented. The TPSi NP with a pore size of 10.7 nm and inorganic framework enables high-efficiency loading of Wnt3a, prolongs Wnt3a release, and increases antioxidative stress activity in the labeled mesenchymal stem cells (MSCs), which are highly beneficial properties for cell protection in stem cell therapy for myocardial infarction. It is confirmed that the intracellular aggregation of TPSi NPs can highly amplify the acoustic scattering of the labeled MSCs, resulting in a 2.3-fold increase in the ultrasound (US) signal compared with that of unlabeled MSCs. The translational potential of the designed nanoagent for real-time US imaging-guided stem cell transplantation is confirmed via intramyocardial injection of labeled MSCs in a nude mouse model. It is proposed that the intracellular aggregation of protein drug-loaded TPSi NPs could be a simple but robust strategy for improving the therapeutic effect of stem cell therapy.

Knockdown of NRAGE induces odontogenic differentiation by activating NF-κB signaling in mouse odontoblast-like cells.

PURPOSE: Neurotrophin receptor-interacting MAGE homologue (Nrage) plays an important role in bone development and the metabolism of normal skeletal structures. Our previous study showed that Nrage inhibited the odontogenic differentiation of mouse dental pulp cells. However, the potential roles and mechanism of Nrage in regulating odontogenic differentiation are unknown. The aim of this study was to investigate the molecular mechanism of Nrage in odontogenic differentiation of mouse odontoblast-like cells. MATERIALS AND METHODS: Endogenous expression of Nrage was stably downregulated by lentivirus-mediated shRNA. Mineralized nodules formation was detected by alizarin red S staining. Dmp-1, Dspp, and ALP mRNA and protein levels were detected by qRT-PCR and western blotting, respectively. In addition, ALPase activity was detected. Confocal microscopy and co-immunoprecipitation (co-IP) were used to analyze the interactions between NRAGE and NF-κB signaling molecules. An IKK inhibitor was also used in the study. RESULTS: NRAGE expression in odontoblasts was downregulated during mouse first maxillary molar development. Moreover, NRAGE expression was downregulated during odontogenic differentiation of odontoblast-like cells. NRAGE knockdown significantly upregulated DMP1 and DSP expression, increased ALPase activity, and promoted mineralized nodule formation. In addition, NRAGE knockdown increased the translocation of NF-κB1 to the nucleus and phosphorylation levels of p65. Co-IP results showed that NRAGE bound to IKKß. Most importantly, the promoting effect of Nrage knockdown on odontoblastic differentiation was reduced after treatment with an IKK inhibitor. CONCLUSIONS: Our data confirmed that NRAGE is an important regulator of odontogenic differentiation of odontoblasts by inhibiting the NF-κB signaling pathway through binding to IKKß. ABBREVIATIONS: Nrage: neurotrophin receptor-interacting MAGE homologue; DSP: dentin sialophospho protein; DMP-1: dentin matrix protein-1; BMP: bone morphogenetic protein; Wnt: wingless; NF-κB: nuclear factor of activated B cells; DAPI: 4',6-diamidino-2-phenylindole; KO: knockout; DPCs: dental pulp cells; AA: ascorbic acid; ß-Gly: ß-glycerophosphate; Dex: dexamethasone; co-IP: co-immunoprecipitation; IκB: inhibitor of NF-κB; IKK: IκB kinase.

Chemical Stability and Antimicrobial Activity of Plasma-Sprayed Cerium Oxide-Incorporated Calcium Silicate Coating in Dental Implants.

PURPOSE: The aim of this study is to investigate the biological activity and antibacterial property of cerium oxide-incorporated calcium silicate coatings (CeO2-CS) in dental implants. MATERIALS AND METHODS: In this study, MC3T3-E1 cells cultured on the plastic, Ti-6Al-4V, and the cerium oxide-incorporated calcium silicate coatings (CeO2-CS) coating served as the blank, control, and CeO2-CS groups, respectively. A cell counting kit-8 (CCK-8) and flow cytometry were used to evaluate the biocompatibility. The osteoblastic differentiation of the MC3T3-E1 cells was also analyzed by quantitative real-time polymerase chain reaction analysis. The CCK-8 and counts of colony-forming units (CFUs) were used to detect the antibacterial activity of the coating on Enterococcus faecalis. The study showed that the cerium oxide-incorporated calcium silicate coating (CeO2-CS) has better biocompatibility. Meanwhile, the ALP, OCN, and BSP mRNA expression levels in the CeO2-CS group were significantly upregulated (P < 0.05). The number of viable bacteria and the CFU results were significantly reduced in the CeO2-CS group (P < 0.05). CONCLUSION: The cerium oxide-incorporated calcium silicate coatings (CeO2-CS) may promote the osteoblastic differentiation of osteoblasts. Meanwhile, the cerium oxide-incorporated calcium silicate coating (CeO2-CS) showed strong antimicrobial activity on E. faecalis, with good biocompatibility.

Cancer stem-like cell related protein CD166 degrades through E3 ubiquitin ligase CHIP in head and neck cancer.

Our previous studies have identified that CD166 works as a cancer stem-like cell (CSC) marker in epithelial cancers with a large repertoire of cellular functions. However, the post-translational regulatory mechanisms underlying CD166 turnover remain elusive. Several independent studies have reported that E3 ubiquitin ligase CHIP revealed significant biological effects through ubiquitin proteasome pathway on some kinds of malignant tumors. With analyzing the effects of CHIP expressions on stem-like cell populations, we found that CHIP represses CSC characteristics mainly targeting the CSC related protein CD166 in head and neck cancer (HNC). To investigate the role and relationship between CD166 and CHIP, HNC tissues and cell lines were used in this study. A significant negative correlation was observed between the expression levels of CHIP and CD166 in HNC patient samples. We also found that CHIP directly regulates the stability of CD166 protein through the ubiquitin proteasome system, which was also identified participating in the regulation of CSC behaviors in HNCs. Our findings demonstrate that CHIP-CD166-proteasome axis participates in regulating CSC properties in HNCs, suggesting that the regulation of CD166 by CHIP could provide new options for diagnosing and treating in the patients with HNCs.

Effect of storage temperature on the viability of human periodontal ligament fibroblasts.

BACKGROUND: The viability of periodontal ligament fibroblasts (PDLF) can affect the long-term prognosis of replanted avulsed teeth. When immediate replantation of an avulsed tooth is not possible, the cells should be incubated in a physiological storage medium instantly to maintain their biological activity. The ability of different storage media to preserve PDLF viability has been previously evaluated. However, few studies have showed the effect of temperature on the viability of PDLF cultured with various storage media in vitro. MATERIAL AND METHODS: This study was designed to measure PDLF activity by CCK-8 assay to compare the effectiveness at 4, 22 (room temperature), and 37°C under various storage media. RESULTS: Statistical analysis demonstrated that tap water, saline, and saliva decreased cell viability as the storage temperature increased. But the temperature played only a minor role on cell viability when cells were incubated in Hank's balanced salt solution (HBSS), Dubelco's modified Eagle's medium (DMEM), or milk. CONCLUSIONS: Within the parameters of this study, it seems that room temperature is adequate for storing the avulsed teeth in HBSS, DMEM, or milk in the extra-alveolar period.

Characteristics of novel Ti-40Nb-xCu alloy and surface treatment with superior antibacterial property and biocompatibility using micro-arc oxidation for dental implants.

Peri-implantitis and insufficient osseointegration are the principal challenges faced by dental implants at present. In order to fabricate dual-function dental implant materials possessing both antibacterial and osteogenic capabilities, this study incorporates the antimicrobial element Cu into the Ti40Nb alloy, developing a novel Ti40Nb-xCu alloy with antibacterial properties. Among them, Ti40Nb3Cu has the best overall performance. Compared to Ti40Nb, the tensile strength increased by 27.97%, reaching 613 MPa. Although the elongation rate has decreased from 23% to 13.5%, the antibacterial rates against S. aureus and P. gingivalis both exceed 85%. Furthermore, the surface of Ti40Nb-xCu alloy was then treated with micro-arc oxidation to enhance its bioactivity, thereby accelerating osseointegration. The results indicated that the MAO treatment retains the antibacterial properties of the Ti40Nb3Cu alloy while significantly promoting bone formation through its introduced porous coating, thus heralding it as a propitious candidate material for dental implant applications.

Multifunctional role of oral bacteria in the progression of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders of varying severity, ultimately leading to fibrosis. This spectrum primarily consists of NAFL and non-alcoholic steatohepatitis. The pathogenesis of NAFLD is closely associated with disturbances in the gut microbiota and impairment of the intestinal barrier. Non-gut commensal flora, particularly bacteria, play a pivotal role in the progression of NAFLD. Notably, Porphyromonas gingivalis, a principal bacterium involved in periodontitis, is known to facilitate lipid accumulation, augment immune responses, and induce insulin resistance, thereby exacerbating fibrosis in cases of periodontitis-associated NAFLD. The influence of oral microbiota on NAFLD via the "oral-gut-liver" axis is gaining recognition, offering a novel perspective for NAFLD management through microbial imbalance correction. This review endeavors to encapsulate the intricate roles of oral bacteria in NAFLD and explore underlying mechanisms, emphasizing microbial control strategies as a viable therapeutic avenue for NAFLD.

Porphyromonas gingivalis as a promotor in the development of the alcoholic liver disease via ferroptosis.

Alcoholic liver disease (ALD) is a liver disease caused by heavy drinking. Porphyromonas gingivalis (P.g), a major cause of periodontitis, whose antibodies are elevated in severe ALD patients in the plasma. The purpose of this study is to further study the role and the molecular mechanism of P.g in the progress of ALD. In this study, saliva of patients with ALD was collected. Then, an animal model of ALD with oral P.g administration was established, pathology of liver and spleen, intestinal microorganisms and metabolites were analyzed. The molecular mechanism of P.g on ALD was analyzed in vitro. ALD and intestinal microflora and metabolite changes were observed more serious in the alcohol and P.g groups than the alcohol group. Moreover, ferroptosis was aggravated by P.g in the liver. Meanwhile, P.g promoted ferroptosis accomplication with alcohol in vitro, which can be reversed by ferroptosis inhibitors. In conclusion, P.g aggravates ALD through exacerbation gut microbial metabolic disorder in mice with alcohol, which maybe depend on ferroptosis activation in hepatocytes. The study provides a new strategy for prevention and treatment of ALD by improving the oral micro-environment.

Co-delivery of ccl19 gene enhances anti-caries DNA vaccine pCIA-P immunogenicity in mice by increasing dendritic cell migration to secondary lymphoid tissues.

AIM: To investigate how co-delivery of the gene encoding C-C chemokine ligand-19 (CCL-19) affected the systemic immune responses to an anti-caries DNA vaccine pCIA-P in mice. METHODS: Plasmid encoding CCL19-GFP fusion protein (pCCL19/GFP) was constructed by inserting murine ccl19 gene into GFP-expressing vector pAcGFP1-N1. Chemotactic effect of the fusion protein on murine dendritic cells (DCs) was assessed in vitro and in vivo using transwell and flow cytometric analysis, respectively. BALB/c mice were administered anti-caries DNA vaccine pCIA-P plus pCCL19/GFP (each 100 µg, im) or pCIA-P alone. Serum level of anti-PAc IgG was assessed with ELISA. Splenocytes from the mice were stimulated with PAc protein for 48 h, and IFN-γ and IL-4 production was measured with ELISA. The presence of pCCL19/GFP in spleen and draining lymph nodes was assessed using PCR. The expression of pCCL19/GFP protein in these tissues was analyzed under microscope and with flow cytometry. RESULTS: The expression level of CCL19-GFP fusion protein was considerably increased 48 h after transfection of COS-7 cells with pCCL19/GFP plasmids. The fusion protein showed potent chemotactic activity on DCs in vitro. The level of serum PAc-specific IgG was significantly increased from 4 to 14 weeks in the mice vaccinated with pCIA-P plus pCCL19/GFP. Compared to mice vaccinated with pCIA-P alone, the splenocytes from mice vaccinated with pCIA-P plus pCCL19/GFP produced significantly higher level of IFN-γ, but IL-4 production had no significant change. Following intromuscular co-delivery, pCCL19/GFP plasmid and fusion protein were detected in the spleen and draining lymph nodes. Administration of CCL19 gene in mice markedly increased the number of mature DCs in secondary lymphoid tissues. CONCLUSION: CCL19 serves as an effective adjuvant for anti-caries DNA vaccine by inducing chemotactic migration of DCs to secondary lymphoid tissues.

Porphyromonas gingivalis is a risk factor for the development of nonalcoholic fatty liver disease via ferroptosis.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease that can eventually lead to liver cirrhosis and hepatocellular carcinoma. Porphyromonas gingivalis (P.g) is the main pathogen that causes periodontal disease, which participates in the development of NAFLD. The purpose of our study was to further study the direct role of P.g in NAFLD and the underlying molecular mechanism. An animal model of oral P.g administration was established, and liver function and pathology in this model were evaluated. The gut microbiome and metabolic products were analysed. Furthermore, the Th17/Treg balance in the spleen and liver was assessed. In our study, NAFLD was observed in all the mice that were orally administered P.g. The gut microbiome and metabolic products were altered after oral P.g administration. P.g and ferroptosis were observed in the livers of the mice after oral P.g administration. Additionally, ferroptosis was observed in hepatocytes in vitro, but it was reversed by ferroptosis inhibitors. In addition, P.g triggered an imbalance in the Th17/Treg ratio in the liver and spleen in vivo. These findings suggest that oral P.g administration directly induced NAFLD in mice, which may be dependent on the ferroptosis of liver cells that occurs through the Th17/Treg imbalance induced by disordered microbial metabolism. Therefore, improving the periodontal environment is a novel treatment strategy for preventing NAFLD.

Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway.

Osteoporosis bears an imbalance between bone formation and resorption, which is strongly related to oxidative stress. The function of leonurine on bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress is still unclear. Therefore, this study was aimed at identifying the protective effect of leonurine on H2O2 stimulated rat BMSCs. We found that leonurine can alleviate cell apoptosis and promote the differentiation ability of rat BMSCs induced by oxidative stress at an appropriate concentration at 10 µM. Meanwhile, the intracellular ROS level and the level of the COX2 and NOX4 mRNA decreased after leonurine treatment in vitro. The ATP level and mitochondrial membrane potential were upregulated after leonurine treatment. The protein level of PINK1 and Parkin showed the same trend. The mitophage in rat BMSCs blocked by 3-MA was partially rescued by leonurine. Bioinformatics analysis and leonurine-protein coupling provides a strong direct combination between leonurine and the PI3K protein at the position of Asp841, Glu880, Val882. In conclusion, leonurine protects the proliferation and differentiation of BMSCs from oxidative stress by activating mitophagy, which depends on the PI3K/Akt/mTOR pathway. The results showed that leonurine may have potential usage in osteoporosis and bone defect repair in osteoporosis patients.

Quercetin protects rat BMSCs from oxidative stress via ferroptosis.

Quercetin has been shown to have a wide range of beneficial effects, such as anti-inflammation, anti-oxidation and immunomodulation. The study was designed to explore the role and molecular mechanisms of quercetin on the protective effect of bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress in vitro. BMSCs were isolated from 4-week-old male Sprague-Dawley rats. Upon H2O2 stimulation in vitro, the effects of quercetin on the proliferation, anti-oxidation and osteogenic differentiation of BMSCs were evaluated by Cell Counting Kit-8, reactive oxygen species analysis, Western blot (WB), real-time PCR (RT-PCR), alkaline phosphatase staining and alizarin red staining. Additionally, ferroptosis-related markers were examined by WB, RT-PCR and Mito-FerroGreen. Finally, PI3K/AKT/mTOR signaling pathway was explored in these processes. We found that quercetin significantly maintained BMSCs viability upon H2O2 stimulation. Quercetin upregulated protein (ALP, OPN and RUNX2) and mRNA (Alp, Opn, Ocn and Runx2) levels of osteogenic markers, downregulated ROS levels and upregulated antioxidative gene expressions (Nrf2, Cat, Sod-1 and Sod-2) compared with the H2O2 group. The ferroptosis in BMSCs was activated after H2O2 stimulation, and the phosphorylation level of PI3K, AKT and mTOR was upregulated in H2O2-stimulated BMSCs. More importantly, quercetin inhibited ferroptosis and the phosphorylation level of PI3K, AKT and mTOR were downregulated after quercetin treatment. We conclude that quercetin maintained the viability and the osteoblastic differentiation of BMSCs upon H2O2 stimulation, potentially via ferroptosis inhibition by PI3K/AKT/mTOR pathway.

Tocopherol attenuates the oxidative stress of BMSCs by inhibiting ferroptosis through the PI3k/AKT/mTOR pathway.

Oxidative stress can induce bone tissue damage and the occurrence of multiple diseases. As a type of traditional medicine, tocopherol has been reported to have a strong antioxidant effect and contributes to osteogenic differentiation. The purpose of this study was to investigate the protective effect of tocopherol on the oxidative stress of rat bone marrow-derived mesenchymal stem cells (BMSCs) and the underlying mechanisms. By establishing an oxidative stress model in vitro, the cell counting kit-8 (CCK-8), reactive oxygen species (ROS) analysis, Western blot (WB), real-time PCR (RT-PCR), alkaline phosphatase (ALP) staining, and Alizarin Red staining (ARS) evaluated the effects of tocopherol on the cell viability, intracellular ROS levels, and osteogenic differentiation in BMSCs. In addition, ferroptosis-related markers were examined via Western blot, RT-PCR, and Mito-FerroGreen. Eventually, the PI3K/AKT/mTOR signaling pathway was explored. We found that tocopherol significantly maintained the cell viability, reduced intracellular ROS levels, upregulated the levels of anti-oxidative genes, promoted the levels of osteogenic-related proteins, and the mRNA of BMSCs stimulated by H2O2. More importantly, tocopherol inhibited ferroptosis and upregulated the phosphorylation levels of PI3K, AKT, and mTOR of BMSCs upon H2O2 stimulation. In summary, tocopherol protected BMSCs from oxidative stress damage via the inhibition of ferroptosis through the PI3K/AKT/mTOR pathway.

Evaluation of antibacterial property and biocompatibility of Cu doped TiO2 coated implant prepared by micro-arc oxidation.

In order to enhance osteogenic differentiation and antibacterial property of dental implants, volcano-shaped microporous TiO2 coatings doped with Cu were fabricated via micro-arc oxidation (MAO) on Ti. Cu-doped coating with different mass ratios of Cu were obtained by changing the concentration of copper acetate in the electrolyte. The structure of Cu-TiO2 coatings were systematically investigated. Element Copper was uniformly distributed throughout the coating. Compared with TiO2 coating, the Cu-doped can further improved proliferation of bone mesenchymal stem cells (BMSCs), facilitated osteogenic differentiation. The bacteriostasis experiments demonstrated that Cu-doped TiO2 coating possess excellent antibacterial property against Staphylococcus aureus (S. aureus) and Porphyromonas gingivalis (P. gingivalis).

Ultrafine particles exposure is associated with specific operative procedures in a multi-chair dental clinic.

Air quality in dental clinics is critical, especially in light of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, given that dental professionals and patients are at risk of regular exposure to aerosols and bioaerosols in dental clinics. High levels of ultrafine particles (UFP) may be produced by dental procedures. This study aimed to quantify ultrafine particles (UFP) concentrations in a real multi-chair dental clinic and compare the levels of UFP produced by different dental procedures. The efficiency of a high-volume evacuator (HVE) in reducing the UFP concentrations during dental procedures was also assessed. UFP concentrations were measured both inside and outside of a dental clinic in Shanghai, China during a 12-day period from July to September 2020. Dental activities were recorded during working hours. The mean (±standard deviation) concentrations of indoor and outdoor UFP during the sampling period were 8,209 (±4,407) counts/cm3 and 15,984 (±7,977) counts/cm3, respectively. The indoor UFP concentration was much higher during working hours (10,057 ± 5,725 counts/cm3) than during non-working hours (7,163 ± 2,972 counts/cm3). The UFP concentrations increased significantly during laser periodontal treatment, root canal filling, tooth drilling, and grinding, and were slightly elevated during ultrasonic scaling or tooth extraction by piezo-surgery. The highest UFP concentration (241,136 counts/cm3) was observed during laser periodontal treatment, followed by root canal filling (75,034 counts/cm3), which showed the second highest level. The use of an HVE resulted in lower number concentration of UFP when drilling and grinding teeth with high-speed handpieces, but did not significantly reduce UFP measured during laser periodontal therapy. we found that many dental procedures can generate high concentration of UFP in dental clinics, which may have a great health impact on the dental workers. The use of an HVE may help reduce the exposure to UFP during the use of high-speed handpieces.

Short-Term Administration of HIV Protease Inhibitor Saquinavir Improves Skull Bone Healing with Enhanced Osteoclastogenesis.

BACKGROUND: Using immunomodulatory methods to address the challenging issue of craniofacial bone repair may be a potentially effective approach. The protease inhibitor saquinavir has been shown to inhibit the inflammatory response by targeting the toll-like receptor 4/myeloid differentiation primary response complex. Independently, inhibition of toll-like receptor 4 or myeloid differentiation primary response led to enhanced skull bone repair. Therefore, the authors aimed to investigate the effects of saquinavir on skull bone healing. METHODS: The effects of saquinavir on skull bone healing were assessed by means of gene expression, histology, immunohistochemistry, and tomography in a mouse calvarial defect model. Subsequently, the role of saquinavir in cell viability, migration, and osteogenic and osteoclastogenic differentiation was also evaluated in vitro. RESULTS: One-week saquinavir administration improved skull bone healing based on micro-computed tomographic and histomorphometric analyses. Compared to the vehicle control, 1-week saquinavir treatment (1) enhanced osteoclast infiltration (tartrate-resistant acid phosphatase staining) at day 7, but not at days 14 and 28; (2) induced more CD206 + M2 macrophage infiltration, but not F4/80 + M0 macrophages at days 7, 14, and 28; and (3) elevated osteoclastogenic gene RANKL (quantitative polymerase chain reaction) expression and other osteogenic and cytokine expression. Furthermore, in vitro data showed that saquinavir administration did not influence MC3T3-E1 cell migration or mineralization, whereas higher concentrations of saquinavir inhibited cell viability. Saquinavir treatment also enhanced the osteoclastic differentiation of bone marrow-derived precursors, and partially reversed high-mobility group box 1-driven osteoclastogenesis inhibition and elevated proinflammatory cytokine expression. CONCLUSION: The improved skull bone repair following short-term saquinavir treatment may involve enhanced osteoclastogenesis and modulated inflammatory response following skull injury. CLINICAL RELEVANCE STATEMENT: The authors' work demonstrates improved skull bone healing by short-term application of saquinavir, a drug traditionally used in the treatment of acquired immunodeficiency syndrome. As such, saquinavir may be repurposed for skeletal repair.