Systemic Immune-Inflammation Index and Systemic Inflammation Response Index are Associated With Periodontitis: Evidence From NHANES 2009 to 2014.

INTRODUCTION AND AIMS: Periodontitis, a chronic inflammatory condition affecting the supporting structures of the teeth, is a substantial public health burrden whilst impacting the life quality of those affected. Elevated levels of systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) have been implicated in various inflammatory conditions. This study aimed to investigate the relationship between SII and SIRI with periodontitis. METHODS: The study examined a total of 8666 participants in the 2009 to 2014 National Health and Nutrition Examination Survey (NHANES). The study compared the weighted prevalence of periodontitis among various groups. The association between SII, SIRI levels, and periodontitis was analyzed using binary logistic regression. Additionally, we explored nonlinear relationships between SII, SIRI, and the prevalence of periodontitis using restricted cubic spline (RCS) plots. RESULTS: Among participants in the fourth quartile (Q4) of SII and SIRI, the highest prevalence of periodontitis was observed, with rates of 44.87% and 48.41%, respectively. After adjusting for all covariates, the odds ratio (OR) for periodontitis associated with SII Q4 was 1.19 (95% CI 1.02, 1.39, P = .03), while for SIRI Q4, it was 1.18 (95% CI 1.01, 1.39, P = .04). In addition, the results of sensitivity analysis revealed consistent findings, indicating that after adjusting for all covariates, the OR for periodontitis associated with SII Q4 and SIRI Q4 remained statistically significant. Specifically, the OR for periodontitis associated with SII Q4 was 1.19 (95% CI 1.02, 1.39, P = .03), while for SIRI Q4, it was 1.19 (95% CI 1.01, 1.40, P = .04). CONCLUSIONS: These results indicate that elevated SII and SIRI levels are associated with an increased prevalence of periodontitis. CLINICAL RELEVANCE: These findings suggest a potential connection between systemic inflammation and periodontitis, highlighting the importance of periodontitis patients being aware of their systemic diseases that are inflammatory in nature such as chronic cardiovascular afflictions.

Corrigendum: Roles of ubiquitin-specific proteases in inflammatory diseases.

[This corrects the article DOI: 10.3389/fimmu.2024.1258740.].

Roles of ubiquitin-specific proteases in inflammatory diseases.

Ubiquitin-specific proteases (USPs), as one of the deubiquitinating enzymes (DUBs) families, regulate the fate of proteins and signaling pathway transduction by removing ubiquitin chains from the target proteins. USPs are essential for the modulation of a variety of physiological processes, such as DNA repair, cell metabolism and differentiation, epigenetic modulations as well as protein stability. Recently, extensive research has demonstrated that USPs exert a significant impact on innate and adaptive immune reactions, metabolic syndromes, inflammatory disorders, and infection via post-translational modification processes. This review summarizes the important roles of the USPs in the onset and progression of inflammatory diseases, including periodontitis, pneumonia, atherosclerosis, inflammatory bowel disease, sepsis, hepatitis, diabetes, and obesity. Moreover, we highlight a comprehensive overview of the pathogenesis of USPs in these inflammatory diseases as well as post-translational modifications in the inflammatory responses and pave the way for future prospect of targeted therapies in these inflammatory diseases.

Corrigendum to "3D-printed tri-element-doped hydroxyapatite/ polycaprolactone composite scaffolds with antibacterial potential for osteosarcoma therapy and bone regeneration" [Bioact. Mater. 31 (January 2024) 18-37].

[This corrects the article DOI: 10.1016/j.bioactmat.2023.07.004.].

3D-printed tri-element-doped hydroxyapatite/ polycaprolactone composite scaffolds with antibacterial potential for osteosarcoma therapy and bone regeneration.

The resection of malignant osteosarcoma often results in large segmental bone defects, and the residual cells can facilitate recurrence. Consequently, the treatment of osteosarcoma is a major challenge in clinical practice. The ideal goal of treatment for osteosarcoma is to eliminate it thoroughly, and repair the resultant bone defects as well as avoid bacterial infections. Herein, we fabricated a selenium/strontium/zinc-doped hydroxyapatite (Se/Sr/Zn-HA) powder by hydrothermal method, and then employed it with polycaprolactone (PCL) as ink to construct composite scaffolds through 3D printing, and finally introduced them in bone defect repair induced by malignant osteosarcoma. The resultant composite scaffolds integrated multiple functions involving anti-tumor, osteogenic, and antibacterial potentials, mainly attributed to the anti-tumor effects of SeO32-, osteogenic effects of Sr2+ and Zn2+, and antibacterial effects of SeO32- and Zn2+. In vitro studies confirmed that Se/Sr/Zn-HA leaching solution could induce apoptosis of osteosarcoma cells, differentiation of MSCs, and proliferation of MC3T3-E1 while showing excellent antibacterial properties. In vivo tests demonstrated that Se/Sr/Zn-HA could significantly suppress tumors after 8 days of injection, and the Se/Sr/Zn-HA-PCLs scaffold repaired femoral defects effectively after 3 months of implantation. Summarily, the Se/Sr/Zn-HA-PCLs composite scaffolds developed in this study were effective for tumor treatment, bone defect repair, and post-operative anti-infection, which provided a great potential to be a facile therapeutic material for osteosarcoma resection.

Association between probiotic consumption and periodontitis: Evidence from NHANES 2009-2014.

AIM: The study aimed to provide evidence of the relationship between probiotics consumption and periodontitis. MATERIALS AND METHODS: A total of 4577 adults who participated in the National Health and Nutrition Examination Survey (NHANES) during 2009-2014 were included in the study. The weighted prevalence of periodontitis was compared among different groups, and a weighted binary logistic regression analysis was conducted to explore the relationship between probiotic consumption and periodontitis. Receiver operating characteristic (ROC) curves were used to assess the role of probiotic consumption in the periodontitis prediction model. RESULTS: Participants who consumed probiotics had a significantly lower prevalence of periodontitis than those who did not (41.08% vs. 27.83%, p < .001). After fully adjusting for all factors, the odds ratio associated with periodontitis for consuming probiotics was 0.70 (95% confidence interval 0.54-0.92, p = .01) when compared with those who did not consume probiotics. A predictive model including age, sex, ethnicity, poverty income ratio, smoking status and probiotics had 77.0% sensitivity and 60.3% specificity in detecting periodontitis in US adults and achieved an area under the ROC curve of 0.749. CONCLUSIONS: These results indicate that consuming probiotics is associated with a reduced risk of periodontitis.

Follicle-stimulating hormone is negatively associated with nonalcoholic fatty liver disease in a Chinese elderly population: a retrospective observational study.

BACKGROUND: Several studies have explored the connection between follicle-stimulating hormone (FSH) and nonalcoholic fatty liver disease (NAFLD). However, the impact of FSH elevation on NAFLD remains a topic of debate. Hence, this investigation aimed to evaluate the potential correlation between FSH levels and NAFLD in the aging population. METHODS: This was a retrospective observational cross-sectional study between July 2017 and August 2018 in our hospital. We used data obtained from 455 patients over 60 years old. Anthropometrics and laboratory tests were performed for each patient. NAFLD was diagnosed by sonographic features and the fatty liver index (LFI). RESULTS: Of the 455 patients, 200 (43.96%) had NAFLD on their ultrasound and 169 (37.14%) had NAFLD according to the LFI. An intraclass correlation coefficient of the two methods was 80.4% (P < 0.001). People with NAFLD on their ultrasound showed lower FSH levels (52.68 vs. 61.39 IU/L) and more unfavorable metabolic profiles. FSH was negatively correlated with age, alanine aminotransferase, estradiol, testosterone, systolic blood pressure, waist, body mass index, fasting blood glucose, postload plasma glucose and positive associated with total cholesterol, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol by Spearman correlation analysis (all P < 0.05). By controlling for all confounding factors, the odds ratios (OR) of FSH for NAFLD were determined in elderly individuals, both men and women, aged 60-70 years and over 70 years. These ORs were found to be 0.937, 0.982, 0.983, and 0.973, respectively, with corresponding 95% confidence intervals (CI) of 0.892-0.984 (P = 0.009), 0.971-0.993 (P = 0.002), 0.967-0.999 (P = 0.033), and 0.958-0.989 (P = 0.001). In addition, our findings demonstrated no significant correlation between FSH and advanced fibrosis when adjusting for potential covariates. The OR for advanced fibrosis was 0.979 (95% CI, 0.938-1.022, P = 0.339). Additionally, ROC curve analysis showed an optimal cut-off value of 66.91 for women and 15.25 for men for NAFLD diagnosis. CONCLUSIONS: There was an inverse relationship observed between levels of FSH in the blood serum and NAFLD in the elderly population. These findings suggest that reduced FSH levels might serve as a potential risk factor or biomarker for NAFLD in the elderly.

TiO2nanotubes promote osteogenic differentiation of human bone marrow stem cells via epigenetic regulation ofRMRP/DLEU2/EZH2 pathway.

TiO2nanotubes (TNTs) significantly promote osteogenic differentiation and bone regeneration of cells. Nevertheless, the biological processes by which they promote osteogenesis are currently poorly understood. Long non-coding RNAs (lncRNAs) are essential for controlling osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Epigenetic chromatin modification is one of the pathways in which lncRNAs regulate osteogenic differentiation. Here, we reported that TNTs could upregulate lncRNARMRP, and inhibition of lncRNARMRPin human BMSCs (hBMSCs) grown on TNTs could decrease runt-related transcription factor 2 (RUNX2), alkaline phosphatase, osteopontin, and osteocalcin (OCN) expression. Furthermore, we discovered that inhibiting lncRNARMRPelevated the expression of lncRNADLEU2, and lncRNADLEU2knockdown promoted osteogenic differentiation in hBMSCs. RNA immunoprecipitation experiments showed that lncRNADLEU2could interact with EZH2 to induce H3K27 methylation in the promoter regions of RUNX2 and OCN, suppressing gene expression epigenetically. According to these results, lncRNARMRPis upregulated by TNTs to promote osteogenic differentiation throughDLEU2/EZH2-mediated epigenetic modifications.

Tuning Water-Resistant Networks in Mussel-Inspired Hydrogels for Robust Wet Tissue and Bioelectronic Adhesion.

Hydrogels with robust wet adhesion are desirable for applications in aqueous environments. Wet adhesion arising from synergy between hydrophobic and catechol components in mussel foot proteins has been highlighted. However, optimizing hydrogels with multiple components is challenging because of their complex structure-property relationships. Herein, high-throughput screening of a series of hydrophobic alkyl monomers and adhesive catechol derivatives was used to systematically develop wet adhesive hydrogels. Short alkyl chains promote wet adhesion by repelling water at the adhesive interface, whereas long alkyl chains form strong hydrophobic interactions inside the hydrogel network that impede or dissipate energy for wet adhesion. The optimized wet adhesive hydrogel, containing short alkyl chain, was applied for rapid hemostasis and wound healing because of the synergistic effect of catechol and alkyl groups and its immunomodulation ability, which is revealed through a transcriptomic analysis. Conductive nanocomponents were incorporated into the optimized hydrogel to produce a wearable device, which was used for continuous monitoring human electrocardiogram (ECG) during swimming, and in situ epicardial ECG on a porcine living and beating heart. This study demonstrated an efficient and generalized molecular design strategy for multifunctional wet adhesive hydrogels.

Epigenetic Regulation of Methylation in Determining the Fate of Dental Mesenchymal Stem Cells.

Dental mesenchymal stem cells (DMSCs) are crucial in tooth development and periodontal health, and their multipotential differentiation and self-renewal ability play a critical role in tissue engineering and regenerative medicine. Methylation modifications could promote the appropriate biological behavior by postsynthetic modification of DNA or protein and make the organism adapt to developmental and environmental prompts by regulating gene expression without changing the DNA sequence. Methylation modifications involved in DMSC fate include DNA methylation, RNA methylation, and histone modifications, which have been proven to exert a significant effect on the regulation of the fate of DMSCs, such as proliferation, self-renewal, and differentiation potential. Understanding the regulation of methylation modifications on the behavior and the immunoinflammatory responses involved in DMSCs contributes to further study of the mechanism of methylation on tissue regeneration and inflammation. In this review, we briefly summarize the key functions of histone methylation, RNA methylation, and DNA methylation in the differentiation potential and self-renewal of DMSCs as well as the opportunities and challenges for their application in tissue regeneration and disease therapy.

Adhesive Gelatin-Catechol Complex Reinforced Poly(Acrylic Acid) Hydrogel with Enhanced Toughness and Cell Affinity for Cartilage Regeneration.

The repair of cartilage damage caused by trauma, wear, or degenerative deformation remains a major challenge in modern medicine. Therefore, it is essential to develop a mechanically compatible and bioactive scaffold for cartilage tissue regeneration. In this study, a mussel-inspired, tough, adhesive polydopamine/gelatin-poly(acrylic acid) (PDA/Gel-PAA) composite hydrogel was developed for cartilage regeneration. The hydrogel achieved a high compressive strength of up to 0.67 MPa and a toughness of 420 J/m2 because of the unique chemical-physical cross-linking structure by introducing the PDA/Gel complex into the PAA network. PAA chains with rich carboxyl groups mimic the negatively charged glycosaminoglycans (GAGs) in the natural cartilage extracellular matrix (ECM), leading to strong water retention in the hydrogel. The incorporation of the PDA/Gel complex with catechol groups on PDA and arginine-glycine-aspartic acid (RGD) sequences on gelatin chains provided abundant adhesive motifs to improve the cell affinity and tissue adhesiveness of PAA, thereby facilitating the adhesion and proliferation of bone marrow stromal cells (BMSCs). In addition, transforming growth factor-ß3 (TGFß3) was stably immobilized and released from the PDA/Gel-PAA hydrogel. Thus, adhesive hydrogels can provide a suitable microenvironment to promote cell migration in the defect area and induce chronogenesis for cartilage regeneration.

Micro/nano-topography promotes osteogenic differentiation of bone marrow stem cells by regulating periostin expression.

Micro/nano-topography (MNT) is an important factor affecting cell response. Earlier studies using titania (TiO2) nanotube as a model of MNT found that they mediated the differentiation of BMSCs into osteoblasts, but the mechanisms are not fully understood. Surprisingly, Periostin (Postn), a secreted protein involved in extracellular matrix (ECM) construction and promoting osteogenic differentiation of bone marrow stem cells (BMSCs), was previously observed to significantly up-regulated on TiO2 nanotube. We proposed that Postn may act as a MNT signal transduction role. In this study, we investigated the effect of MNT on Postn, and the influence of Postn on osteogenic differentiation-related genes through focal adhesion and downstream signals. It was found that, titanium (Ti) plates carrying TiO2 nanotubes with diameters of ∼100 nm (TNT-100) significantly up-regulated the expression of Postn compared with flat Ti. Furthermore, Postn activated the downstream focal adhesion kinase (FAK) signal pathway and ß-catenin into the nucleus by interacting with integrin αV. Surprisingly, TNT-100 up-regulated the transcription level of Wnt3a, which was independent of the up-regulation of Postn. This new Postn signaling pathway may provide more insights into the signal transduction mechanism of MNT and development of biomaterials with improved osteogenic properties.

Preparation of multigradient hydroxyapatite scaffolds and evaluation of their osteoinduction properties.

Porous hydroxyapatite (HA) scaffolds are often used as bone repair materials, owing to their good biocompatibility, osteoconductivity and low cost. Vascularization and osteoinductivity of porous HA scaffolds were limited in clinical application, and these disadvantages were need to be improved urgently. We used water-in-oil gelation and pore former methods to prepare HA spheres and a porous cylindrical HA container, respectively. The prepared HA spheres were filled in container to assemble into composite scaffold. By adjusting the solid content of the slurry (solid mixture of chitin sol and HA powder) and the sintering temperature, the porosity and crystallinity of the HA spheres could be significantly improved; and mineralization of the HA spheres significantly improved the biological activity of the composite scaffold. The multigradient (porosity, crystallinity and mineralization) scaffold (HA-700) filled with the mineralized HA spheres exhibited a lower compressive strength; however, in vivo results showed that their vascularization ability were higher than those of other groups, and their osteogenic Gini index (Go: an index of bone mass, and inversely proportional to bone mass) showed a continuous decrease with the implantation time. This study provides a new method to improve porous HA scaffolds and meet the demands of bone tissue engineering applications.

Bioadhesive injectable hydrogel with phenolic carbon quantum dot supported Pd single atom nanozymes as a localized immunomodulation niche for cancer catalytic immunotherapy.

Immunotherapy is a powerful way to treat cancer, however, systemic treatment-associated adverse effects remain a major concern. In this study, a bioadhesive injectable hydrogel is developed to provide localized immune niches for tumor microenvironment immunomodulation and cancer catalytic immunotherapy. First, a phenolic single atom nanozyme (SAN) was developed by in situ synthesis of Pd single atom on catechol-grafted carbon-quantum-dot (DA-CQD@Pd) templates. Then, the bioadhesive injectable hydrogel consisting of DA-CQD@Pd SAN and immune adjuvant CpGODN was formed through SAN-catalyzed free-radical polymerization. The SAN exhibited peroxidase-like activity to generate ROS and kill tumor cells through catalytic therapy. The hydrogel locally released CpGODN in a sustained manner, which limited the risk of systemic exposure, reducing the impact of CpGODN toxicity, and protecting CpGODN from degradation. The bioadhesive hydrogel immobilized around solid tumor to provide an immune response site after injection. When combined it with the administration of immune checkpoint inhibitor anti-PD-L1, the hydrogel realized localized immunomodulation, maximized therapeutic efficacy and prevents tumor metastasis via a catalytic immunotherapy.

Environmentally favorable magnesium phosphate anti-corrosive coating on carbon steel and protective mechanisms.

Polymer coatings are commonly used to protect carbon steels from corrosion but they are susceptible to weathering and many of them have environmental concerns. Therefore, we studied the possibility of an environmentally favorable inorganic magnesium phosphate cement (MPC) coating for protecting mild steel. A formulation suitable for coating steel was developed by compositional modification [i.e., incremental replacement of dead-burned magnesia (MgO) with magnesium hydroxide (Mg(OH)2)] to a road-repair MPC. This modification yielded an acceptable working time and prevented pore formation at the coating-steel interface. Corrosion monitoring by linear polarization and electrochemical impedance spectroscopy for 14 days found that, the MPC coating substantially increased the linear polarization resistance (Rp) [e.g., day 1: (8.2 ± 1.7) × 103 (nadir value) vs. 495 ± 55 Ω cm-2] and charge transfer resistance (Rct) (e.g., day 1: 9.3 × 103 vs. 3.8 × 102 Ω cm-2). The coated steel underwent neutral sodium chloride (NaCl) salt spray for 2400 h without visible rusting. Immersion for 24 h in liquids simulating the pore fluid indicated that, passivation by the excess MgO in the coating was a major contributor to its anti-corrosive property. Tafel polarization in the liquids found that, corrosion current density (Icorr) followed the rank: 3.5% NaCl solution (6.0 µA cm-2) > 3.5% NaCl solution containing MgO (3.6 µA cm-2) > 3.5% NaCl solution containing fragmented MPC (1.7 µA cm-2), suggesting that a physical barrier effect and dissolved phosphate ions improved its protection. This study shows that, MPC coating is a promising durable and environmentally favorable anti-corrosive material for protecting steel structures in some applications.

EnhFFL: A database of enhancer mediated feed-forward loops for human and mouse.

Feed-forward loops (FFLs) are thought to be one of the most common and important classes of transcriptional network motifs involved in various diseases. Enhancers are cis-regulatory elements that positively regulate protein-coding genes or microRNAs (miRNAs) by recruiting DNA-binding transcription factors (TFs). However, a comprehensive resource to identify, store, and analyze the FFLs of typical enhancer and super-enhancer FFLs is not currently available. Here, we present EnhFFL, an online database to provide a data resource for users to browse and search typical enhancer and super-enhancer FFLs. The current database covers 46 280/7000 TF-enhancer-miRNA FFLs, 9997/236 enhancer-miRNA-gene FFLs, 3 561 164/3 193 182 TF-enhancer-gene FFLs, and 1259/235 TF-enhancer feed-back loops (FBLs) across 91 tissues/cell lines of human and mouse, respectively. Users can browse loops by selecting species, types of tissue/cell line, and types of FFLs. EnhFFL supports searching elements including name/ID, genomic location, and the conservation of miRNA target genes. We also developed tools for users to screen customized FFLs using the threshold of q value as well as the confidence score of miRNA target genes. Disease and functional enrichment analysis showed that master miRNAs that are widely engaged in FFLs including TF-enhancer-miRNAs and enhancer-miRNA-genes are significantly involved in tumorigenesis. Database URL:http://lcbb.swjtu.edu.cn/EnhFFL/.

Distributions of eight bioactive components in rat tissues administered Marsdenia tenacissima extract orally detected through UPLC-MS/MS.

Marsdenia tenacissima (Roxb.) Wight et Arn. (M. tenacissima) is considered an anticancer medicine in traditional Chinese medicine, which is extensively used in clinical application since it has great therapeutic effects. Currently, although a number of articles have examined M. tenacissima in terms of its pharmacology and quality control, few have investigated the in vivo mechanism of M. tenacissima active ingredients. Previously, we have studied the pharmacokinetics of eight active ingredients after oral administration of M. tenacissima extracts in rat plasma. This study constructed a new scientific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach to simultaneously quantify the contents of tenacissosides B, G, H and I, cryptochlorogenic acid, chlorogenic acid, neochlorogenic acid and caffeic acid in rats orally administered M. tenacissima extract. The proposed approach was successfully used for investigating the distributions of those eight analytes in rat tissues, with digoxin being used as an internal control. The Eclipse Plus C18 RRHD column was used for determination at a column temperature of 30°C. The mobile phase system consisted of acetonitrile and water (supplemented with 0.1% formic acid) under optimal gradient elution conditions. Afterwards, this approach was validated according to the requirements for the analysis of biological samples developed by the US Food and Drug Administration, including precision, accuracy, stability and matrix effects. Based on tissue distribution analysis, those eight analytes showed rapid distribution within all the tested tissues. With regard to organic acid distribution, it followed the order stomach > liver > kidney > small intestine > lung > spleen > heart, whereas the four steroids followed the order stomach > lung > spleen > small intestine > liver > kidney > heart. The present study lays the theoretical foundation for the use and development of M. tenacissima in clinical practice.

Fibrinogen-to-Albumin Ratio Predicts Contrast-Induced Nephropathy in Patients after Emergency Percutaneous Coronary Intervention.

BACKGROUND: The aim of the present study was to investigate the association between fibrinogen-to-albumin ratio (FAR) with contrast-induced nephropathy (CIN) in patients undergoing emergency percutaneous coronary intervention (PCI). METHODS: 565 patients with emergency PCI were consecutively enrolled. The primary outcome was CIN defined as either a 25% increase in baseline serum creatinine levels or a 0.5 mg/dL (44 µmol/L) increase in absolute serum creatinine levels within 72 h after the contrast medium exposure. Logistic regression analysis was applied to analyze whether FAR was an independent risk factor for CIN. RESULTS: Overall, 29 (5.1%) patients developed CIN. Compared with the patients without CIN, the patients developing CIN had lower albumin (39.79 ± 3.95 vs. 37.14 ± 5.21, P=0.012) and higher fibrinogen levels (3.51 ± 0.94 vs. 4.14 ± 0.96, P < 0.001). In the multivariate logistic analysis, FAR was an independent predictor of CIN (OR = 3.97; 95% CI, 1.61-9.80; P=0.003) along with perihypotension, age >75 years, and LVEF <45%, and 0.106 was the optimal cutoff value of preprocedural FAR to predict CIN. CONCLUSION: Preprocedural levels of FAR were associated with CIN in patients after emergency PCI.

AMOT130/YAP pathway in topography-induced BMSC osteoblastic differentiation.

Micro/nano-topography (MNT) is an important variable affecting osseointegration of bone biomaterials, but the underlying mechanisms are not fully understood. We probed the role of a AMOT130/YAP pathway in osteoblastic differentiation of bone marrow mesenchymal stems cultured on titanium (Ti) carrying MNTs. Ti surfaces with two well-defined MNTs (TiO2 nanotubes of different diameters and wall thicknesses) were prepared by anodization. Rat BMSCs were cultured on flat Ti and Ti surfaces carrying MNTs, and cell behaviors (i.e., morphology, F-actin development, osteoblastic differentiation, YAP localization) were studied. Ti surfaces carrying MNTs increased F-actin formation, osteoblastic gene expression, and protein AMOT130 production in BMSCs (all vs. flat Ti), and the surface carrying larger nantubes was more effective, confirming osteoblastic differentiation induced by MNTs. Elevation of the AMOT130 level (by inhibiting its degradation) increased the osteoblastic gene expression, F-actin formation, and nuclear localization of YAP. These show that, AMOT130/YAP is an important pathway mediating the translation of MNT signals to BMSC osteoblastic commitment, likely via the cascade: AMOT130 promotion of F-actin formation, increased YAP nuclear import, and activation of osteoblastic gene expression.