The role of the Piezo1 channel in osteoblasts under cyclic stretching: A study on osteogenic and osteoclast factors.

OBJECTIVES: Orthodontic tooth movement is a mechanobiological reaction induced by appropriate forces, including bone remodeling. The mechanosensitive Piezo channels have been shown to contribute to bone remodeling. However, information about the pathways through which Piezo channels affects osteoblasts remains limited. Thus, we aimed to investigate the influence of Piezo1 on the osteogenic and osteoclast factors in osteoblasts under mechanical load. MATERIALS AND METHODS: Cyclic stretch (CS) experiments on MC3T3-E1 were conducted using a BioDynamic mechanical stretching device. The Piezo1 channel blocker GsMTx4 and the Piezo1 channel agonist Yoda1 were used 12 h before the application of CS. MC3T3-E1 cells were then subjected to 15% CS, and the expression of Piezo1, Piezo2, BMP-2, OCN, Runx2, RANKL, p-p65/p65, and ALP was measured using quantitative real-time polymerase chain reaction, western blot, alkaline phosphatase staining, and immunofluorescence staining. RESULTS: CS of 15% induced the highest expression of Piezo channel and osteoblast factors. Yoda1 significantly increased the CS-upregulated expression of Piezo1 and ALP activity but not Piezo2 and RANKL. GsMTx4 downregulated the CS-upregulated expression of Piezo1, Piezo2, Runx2, OCN, p-65/65, and ALP activity but could not completely reduce CS-upregulated BMP-2. CONCLUSIONS: The appropriate force is more suitable for promoting osteogenic differentiation in MC3T3-E1. The Piezo1 channel participates in osteogenic differentiation of osteoblasts through its influence on the expression of osteogenic factors like BMP-2, Runx2, and OCN and is involved in regulating osteoclasts by influencing phosphorylated p65. These results provide a foundation for further exploration of osteoblast function in orthodontic tooth movement.

Skeleton-derived extracellular vesicles in bone and whole-body aging: From mechanisms to potential applications.

The skeleton serves as a supportive and protective organ for the body. As individuals age, their bone tissue undergoes structural, cellular, and molecular changes, including the accumulation of senescent cells. Extracellular vesicles (EVs) play a crucial role in aging through the cellular secretome and have been found to induce or accelerate age-related dysfunction in bones and to contribute further via the circulatory system to the aging of phenotypes of other bodily systems. However, the extent of these effects and their underlying mechanisms remain unclear. Therefore, this paper attempts to give an overview of the current understanding of age-related alteration in EVs derived from bones. The role of EVs in mediating communications among bone-related cells and other body parts is discussed, and the significance of bones in the whole-body aging process is highlighted. Ultimately, it is hoped that gaining a clearer understanding of the relationship between EVs and aging mechanisms may serve as a basis for new treatment strategies for age-related degenerative diseases in the skeleton and other systems.

M2 macrophages secrete glutamate-containing extracellular vesicles to alleviate osteoporosis by reshaping osteoclast precursor fate.

Osteoclast precursors (OCPs) are thought to commit to osteoclast differentiation, which is accelerated by aging-related chronic inflammation, thereby leading to osteoporosis. However, whether the fate of OCPs can be reshaped to transition into other cell lineages is unknown. Here, we showed that M2 macrophage-derived extracellular vesicles (M2-EVs) could reprogram OCPs to downregulate osteoclast-specific gene expression and convert OCPs to M2 macrophage-like lineage cells, which reshaped the fate of OCPs by delivering the molecular metabolite glutamate. Upon delivery of glutamate, glutamine metabolism in OCPs was markedly enhanced, resulting in the increased production of α-ketoglutarate (αKG), which participates in Jmjd3-dependent epigenetic reprogramming, causing M2-like macrophage differentiation. Thus, we revealed a novel transformation of OCPs into M2-like macrophages via M2-EVs-initiated metabolic reprogramming and epigenetic modification. Our findings suggest that M2-EVs can reestablish the balance between osteoclasts and M2 macrophages, alleviate the symptoms of bone loss, and constitute a new approach for bone-targeted therapy to treat osteoporosis.

The interaction between the nervous system and the stomatognathic system: from development to diseases.

The crosstalk between the nerve and stomatognathic systems plays a more important role in organismal health than previously appreciated with the presence of emerging concept of the "brain-oral axis". A deeper understanding of the intricate interaction between the nervous system and the stomatognathic system is warranted, considering their significant developmental homology and anatomical proximity, and the more complex innervation of the jawbone compared to other skeletons. In this review, we provide an in-depth look at studies concerning neurodevelopment, craniofacial development, and congenital anomalies that occur when the two systems develop abnormally. It summarizes the cross-regulation between nerves and jawbones and the effects of various states of the jawbone on intrabony nerve distribution. Diseases closely related to both the nervous system and the stomatognathic system are divided into craniofacial diseases caused by neurological illnesses, and neurological diseases caused by an aberrant stomatognathic system. The two-way relationships between common diseases, such as periodontitis and neurodegenerative disorders, and depression and oral diseases were also discussed. This review provides valuable insights into novel strategies for neuro-skeletal tissue engineering and early prevention and treatment of orofacial and neurological diseases.

Fe-Gd Ferromagnetic Cyclic Coordination Cluster [FeIII4GdIII4(teaH)8(N3)8(H2O)] with Magnetic Anisotropy─Theory and Experiment.

The synthesis, structural, and magnetic characterization of [FeIII4LnIII4(teaH)8(N3)8(H2O)] (Ln = Gd and Y) and the previously reported isostructural Dy analogue are discussed. The commonly held belief that both FeIII and GdIII can be regarded as isotropic ions is shown to be an oversimplification. This conclusion is derived from the magnetic data for the YIII analogue in terms of the zero-field splitting seen for FeIII and from the fact that the magnetic data for the new GdIII analogue can only be fit employing an additional anisotropy term for the GdIII ions. Furthermore, the Fe4Gd4 ring shows slow relaxation of magnetization. Our analysis of the experimental magnetic data employs both density functional theory as well as the finite-temperature Lanczos method which finally enables us to provide an almost perfect fit of magnetocaloric properties.

Regulating Chemistry Composition on a Crystal Surface by Introducing a Cation Trapping Agent: A Novel Strategy to Tune Moisture Sensitivity of Crystals.

The crystal moisture sensitivity can be tuned by the chemical composition on the crystal surface. Ammonium dinitramide (ADN) crystal is a promising oxidizer for solid propellants. However, its strong moisture sensitivity greatly limits its practical applications. Here, we report a novel strategy to reduce moisture sensitivity by trapping ammonium cations with montmorillonite (MMT) to modulate the chemistry composition on the ADN crystal surface. An extraordinary phenomenon can be found: the crystal surface of the recrystallized ADN with 1% MMT (ADN-1% MMT) is rearranged with more low-surface-energy -NO2 groups (65.84%) and less high-surface-energy NH4+ groups (4.8%). In addition, ADN-1% MMT presents a more homogeneous low surface energy feature with a narrower surface energy distribution. As a result, ADN-1% MMT exhibits a noticeably lower hygroscopicity at 20 °C and 60% RH, which is accordant with the simulated hygroscopicity based on XRD and moisture sensitivity prediction based on surface energy. This study brings out a novel modification idea to adjust crystal moisture sensitivity by tuning the chemistry composition on the crystal surface based on trapping cations.

Intrafibrillar Mineralization and Immunomodulatory for Synergetic Enhancement of Bone Regeneration via Calcium Phosphate Nanocluster Scaffold.

Inspired by the bionic mineralization theory, organic-inorganic composites with hydroxyapatite nanorods orderly arranged along collagen fibrils have attracted extensive attention. Planted with an ideal bone scaffold will contribute greatly to the osteogenic microenvironment; however, it remains challenging to develop a biomimetic scaffold with the ability to promote intrafibrillar mineralization and simultaneous regulation of immune microenvironment in situ. To overcome these challenges, a scaffold containing ultra-small particle size calcium phosphate nanocluster (UsCCP) is prepared, which can enhance bone regeneration through the synergetic effect of intrafibrillar mineralization and immunomodulatory. By efficient infiltration into collagen fibrils, the UsCCP released from the scaffold achieves intrafibrillar mineralization. It also promotes the M2-type polarization of macrophages, leading to an immune microenvironment with both osteogenic and angiogenic potential. The results confirm that the UsCCP scaffold has both intrafibrillar mineralization and immunomodulatory effects, making it a promising candidate for bone regeneration.

Accuracy evaluation of cone beam computed tomography applied to measure peri-implant bone thickness in living patients: an ex vivo and in vivo experiment.

OBJECTIVES: This study aims to study the accuracy of cone beam computed tomography (CBCT) for measuring peri-implant bone thickness in living patients via a novel visualization method (NVM). MATERIAL AND METHODS: The validity of the NVM was verified ex vivo by measuring the same peri-implant bone thicknesses in bovine ribs by using raw postoperative CBCT (clinical measurement, CM), the visualized fused images obtained using the NVM (visualized fused measurement, VF), and hard tissue sections (gold standard measurement, GS). The NVM was applied by deconstructing the postoperative CBCT model into the Modelpost-bone and Modelimplant and replacing it with bone from preoperative CBCT and standard implant models, respectively. In vivo, 52 implants were included, and the VF of each implant was obtained using data processing methods similar to those used ex vivo. Then, we compared the results of CM and VF. RESULTS: Ex vivo, the VF was similar to GS, while CM usually underestimated the peri-implant bone thickness, especially at the implant shoulder (P < 0.01). In vivo, on CBCT, areas with a peri-implant bone thickness of 0-0.50 mm were not visible, while those with a thickness of 0.50-1.00 mm were occasionally visible. There was less underestimation of bone along the implant long axis. CONCLUSIONS: Thin peri-implant bones could be completely underestimated on CBCT. CBCT scans alone are insufficient to warrant surgical intervention. Our NVM facilitates the accurate visual assessment of implant dimensions. CLINICAL RELEVANCE: The thickness of peri-implant bone could be completely underestimated when thinner than 1.0 mm in living patients. Familiarity with these confusing CBCT results may help clinicians and patients avoid further unnecessary evaluation, misdiagnosis, and invasive treatment.

Extracellular Vesicles in Bone Homeostasis: Emerging Mediators of Osteoimmune Interactions and Promising Therapeutic Targets.

An imbalance in bone homeostasis results in bone loss and poor healing in bone diseases and trauma. Osteoimmune interactions, as a key contributor to bone homeostasis, depend on the crosstalk between mesenchymal stem cell-osteoblast (MSC-OB) and monocyte-macrophage (MC-Mφ) lineages. Currently, extracellular vesicles (EVs) are considered to be involved in cell-to-cell communication and represent a novel avenue to enhance our understanding of bone homeostasis and to develop novel diagnostic and therapeutic options. In this comprehensive review, we aim to present recent advances in the study of the effect of MC-Mφ-derived EVs on osteogenesis and the regulatory effects of MSC-OB-derived EVs on the differentiation, recruitment and efferocytosis of Mφ. Furthermore, we discuss the role of EVs as crucial mediators of the communication between these cell lineages involved in the development of common bone diseases, with a focus on osteoporosis, osteoarthritis, bone fracture, and periodontal disease. Together, this review focuses on the apparent discrepancies in current research findings and future directions for translating fundamental insights into clinically relevant EV-based therapies for improving bone health.

Preparation and Characterization of TCPP-CaMMT Nanocompound and Its Composite with Polypropylene.

Based on the molecular dynamics method, the tris-(1-chloropropan-2yl) phosphate (TCPP)/montmorillonite (MMT) molecular model was established to study the binding energy and microstructure changes in TCPP and MMT. The theoretical simulation results showed that TCPP can enter the MMT layer and increase the layer spacing. From this, an organic intercalated Ca-montmorillonite TCPP-CaMMT was prepared by a very simple direct mixing method using flame retardant TCPP as a modifier. Polypropylene (PP) composites were prepared by TCPP, CaMMT, and TCPP-CaMMT. The microstructures of TCPP-CaMMT nanocompounds and PP composites were studied by X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM). The results showed that TCPP-CaMMT nanocompounds could be exfoliated into nanosheets in PP. The flame retardancy and mechanical properties of PP/TCPP-CaMMT samples were studied by limited oxygen index (LOI) measurements and tensile tests. The PP/TCPP-CaMMT composites showed better LOI, tensile strength, and elongation at break than the machine-mixed PP/TCPP + CaMMT.

KLF6 facilitates differentiation of odontoblasts through modulating the expression of P21 in vitro.

Multiple signaling pathways are involved in the regulation of cell proliferation and differentiation in odontogenesis and dental tissue renewal, but the details of these mechanisms remain unknown. Here, we investigated the expression patterns of a transcription factor, Krüppel-like factor 6 (KLF6), during the development of murine tooth germ and its function in odontoblastic differentiation. KLF6 was almost ubiquitously expressed in odontoblasts at various stages, and it was co-expressed with P21 (to varying degrees) in mouse dental germ. To determine the function of Klf6, overexpression and knockdown experiments were performed in a mouse dental papilla cell line (iMDP-3). Klf6 functioned as a promoter of odontoblastic differentiation and inhibited the proliferation and cell cycle progression of iMDP-3 through p21 upregulation. Dual-luciferase reporter assay and chromatin immunoprecipitation showed that Klf6 directly activates p21 transcription. Additionally, the in vivo study showed that KLF6 and P21 were also co-expressed in odontoblasts around the reparative dentin. In conclusion, Klf6 regulates the transcriptional activity of p21, thus promoting the cell proliferation to odontoblastic differentiation transition in vitro. This study provides a theoretical basis for odontoblast differentiation and the formation of reparative dentine regeneration.

Extracellular vesicles derived from neural EGFL-Like 1-modified mesenchymal stem cells improve acellular bone regeneration via the miR-25-5p-SMAD2 signaling axis.

Stem cell based transplants effectively regenerate tissues; however, limitations such as immune rejection and teratoma formation prevent their application. Extracellular vesicles (EVs)-mediated acellular tissue regeneration is a promising alternative to stem cell based transplants. Although neural EGFL-like 1 (Nell1) is known to contribute to the osteogenic differentiation of bone marrow stem cells (BMSCs), it remains unknown whether EVs are involved in this process. Here, we present that EVs derived from Nell1-modified BMSCs (Nell1/EVs) have a stronger ability to promote BMSC osteogenesis owing to miR-25-5p downregulation. MiR-25-5p inhibits osteogenesis by targeting Smad2 and suppressing the SMAD and extracellular signal-related kinase 1 and 2 (ERK1/2) pathway activation. In addition, we demonstrate that the 3D-Nell1/EV-hydrogel system is beneficial for bone regeneration in vivo, probably stemming from a slow, continuous release and high concentration of EVs in the bone defect area. Thus, our results have shown the potential of Nell1/EVs as a novel acellular bone regeneration strategy. Mechanistically, the identification of miR-25-5p-SMAD2 signaling axis expands the knowledge of Nell1/EVs induced osteogenesis.

Exosomes Enhance Adhesion and Osteogenic Differentiation of Initial Bone Marrow Stem Cells on Titanium Surfaces.

Successful osseointegration involves the biological behavior of bone marrow stem cells (BMSCs) on an implant surface; however, the role of BMSC-derived extracellular vesicles (EVs)/exosomes in osseointegration is little known. This study aimed to: (i) explore the interaction force between exosomes (Exo) and cells on a titanium surface; (ii) discuss whether the morphology and biological behavior of BMSCs are affected by exosomes; and (iii) preliminarily investigate the mechanism by which exosomes regulate cells on Ti surface. Exosomes secreted by rat BMSCs were collected by ultracentrifugation and analyzed using transmission electron microscopy and nanoparticle tracking analysis. Confocal fluorescence microscopy, scanning electron microscopy, Cell Counting Kit-8 (CCK-8), quantitative real-time polymerase chain reaction techniques, and alkaline phosphatase bioactivity, Alizarin Red staining, and quantification were used to investigate the exosomes that adhere to the Ti plates under different treatments as well as the morphological change, adhesion, spread, and differentiation of BMSCs. We found that exosomes were efficiently internalized and could regulate cell morphology and promoted the adhesion, spreading, and osteogenic differentiation of BMSCs. These were achieved partly by activating the RhoA/ROCK signaling pathway. Our discovery presents a new insight into the positive regulatory effect of exosomes on the biological behaviors of BMSCs on Ti surface and provides a novel route to modify the surface of a Ti implant.

Di- and Tri-nuclear VIII and CrIII Complexes of Dipyridyltriazoles: Ligand Rearrangements, Mixed Valency and Ferromagnetic Coupling.

The first dinuclear and trinuclear chromium(III) and dinuclear vanadium(III) complexes of N 4-R-substituted-3,5-di(2-pyridyl)-1,2,4-triazole (Rdpt) ligands have been prepared by solvothermal complexations under inert atmospheres, and characterized. The reactions of CrIII and VIII with adpt (R = amino) resulted in deamination of the ligand and yielded the dinuclear doubly-triazolate bridged complexes [ V 2 III (dpt -)2Cl4] (1) and [ Cr 2 III (dpt -)2Cl4] (2). In the case of the CrIII complex 2 this bridging results in a rare example of ferromagnetic coupling for a dinuclear CrIII compound. DFT studies confirm that in 2 the ferromagnetic coupling pathways dominate over the antiferromagnetic pathways, whereas in 1 the reverse occurs, consistent with the observed overall antiferromagnetic coupling in that case. It was also found that the use of different additives in the reaction allows the nuclearity of the CrIII product to be manipulated, giving either the dinuclear system, or the first example of a trinuclear circular helicate for a Rdpt complex, [ Cr 3 III (dpt)3Cl6]·1¾MeCN·»DCM (3). Reaction of N 4 -pydpt (R = 4-pyridyl) with VIII led to an unusual shift of the pyridyl substituent from N 4 to N 1 of the triazole, forming the ligand isomer N 1 -pydpt, and giving a dinuclear doubly-triazole bridged complex, [ V 2 III ( N 1 -pydpt)2Cl6]·2MeCN (4). Reaction with CrIII results in loss of the 4-pyridyl ring and a mixture of the di- and trinuclear complexes, 2 and 3. Interestingly, partial oxidation of the VIII in dinuclear complex 4 to vanadyl VIV=O was identified by crystallographic analysis of partially oxidized single crystals, [(VIVO)0.84(VIII)1.16( N 1 -pydpt)2Cl5.16]·0.84H2O·1.16MeCN (5).

Understanding the Superior Stability of Single-Molecule Magnets on an Oxide Film.

The stability of magnetic information stored in surface adsorbed single-molecule magnets is of critical interest for applications in nanoscale data storage or quantum computing. The present study combines X-ray magnetic circular dichroism, density functional theory and magnetization dynamics calculations to gain deep insight into the substrate dependent relevant magnetization relaxation mechanisms. X-ray magnetic circular dichroism reveals the opening of a butterfly-shaped magnetic hysteresis of DyPc2 molecules on magnesium oxide and a closed loop on the bare silver substrate, while density functional theory shows that the molecules are only weakly adsorbed in both cases of magnesium oxide and silver. The enhanced magnetic stability of DyPc2 on the oxide film, in conjunction with previous experiments on the TbPc2 analogue, points to a general validity of the magnesium oxide induced stabilization effect. Magnetization dynamics calculations reveal that the enhanced magnetic stability of DyPc2 and TbPc2 on the oxide film is due to the suppression of two-phonon Raman relaxation processes. The results suggest that substrates with low phonon density of states are beneficial for the design of spintronics devices based on single-molecule magnets.

Study on Interaction between Propargyl-Terminated Polybutadiene and Plasticizers Based on Simulation and Experiments.

Molecular dynamics (MD) simulation and experimental methods are used to explore the interaction between the propargyl-terminated polybutadiene (PTPB) binder and plasticizers bis(2,2-dinitropropyl) formal/acetal (BDNPF/A) and dioctyl sebacate (DOS). Flory-Huggins parameters, radial distribution functions, and binding energies between PTPB and plasticizers are calculated using MD simulations. The solubility parameters of PTPB and the plasticizers are calculated by both MD and group contribution method. The mesoscopic dynamics (MesoDyn) is used to simulate the meso-morphology of PTPB and plasticizer blends by converting the results of MD simulation into MesoDyn simulation parameters. The results of simulations and calculations show that PTPB has better compatibility with DOS than with BDNPF/A, and DOS is more suitable as a plasticizer for PTPB. The results of dynamic rheological experiments show that BDNPF/A has little effect on the dynamic viscosity of PTPB, and DOS can significantly reduce the dynamic viscosity of PTPB and has better plasticizing effect on PTPB. Differential scanning calorimetry and dynamic mechanical analysis tests indicate that the DOS and PTPB blend has only one glass transition temperature, while the PTPB and BDNPF/A blend has two glass transition temperatures. Both simulations and experimental results show that the PTPB binder have better compatibility with DOS than with BDNPF/A, and DOS has better plasticization effects on the PTPB binder.

NEMO­binding domain peptide ameliorates inflammatory bone destruction in a Staphylococcus aureus­induced chronic osteomyelitis model.

Osteomyelitis, which is characterized by progressive inflammatory bone destruction and resorption, is a difficult­to­treat infection. Staphylococcus aureus (S. aureus) is one of the major causes of this disease. This pathogenic microorganism possesses several characteristics, which facilitate its involvement in the occurrence and progression of osteomyelitis. A cell­permeable peptide inhibitor of the IκB kinase complex, the nuclear factor (NF)­κB essential modulator­binding domain (NBD) peptide, has been reported to block osteoclastogenesis and may be considered a potential strategy for preventing inflammatory bone resorption. However, it remains to be determined as to whether the NBD peptide can regulate inflammation and bone resorption in S. aureus­induced osteomyelitis. In order to investigate the role of NBD in S. aureus­induced osteomyelitis, the present study obtained the NBD peptide, and confirmed that it inhibited receptor activator of NF­κB ligand­induced osteoclastogenesis in vitro. Subsequently, a bone defect was generated and S. aureus was injected into the mandible of experimental animals, in order to establish an in vivo osteomyelitis model. The present study analyzed the following three experimental groups: Untreated, treated with debridement, and treated with debridement plus NBD peptide administration. The results revealed that treatment with the NBD peptide reduced the bone defect in a 3­dimensional manner, and reduced bone resorption. To the best of our knowledge, the present study is the first to demonstrate that, in a model of osteomyelitis caused by S. aureus, the NBD peptide serves a role in inhibiting osteolysis and promoting bone remodeling in the direction of osteogenesis. The effects were better than those produced by debridement alone, thus suggesting that it may have promising therapeutic potential in osteomyelitis.

A belt-like one-dimensional Dy chain exhibiting slow magnetic relaxation behavior.

A unique belt-like one-dimensional Dy chain linked through hydroxyl groups was synthesized and structurally characterized. Magnetic studies showed that this Dy chain exhibited significant frequency-dependent ac behavior and clear hysteresis loop below 0.6 K.