Periodontal ligament stem cells (PDLSCs) possess self-renewal, multilineage differentiation, and immunomodulatory properties. They play a crucial role in maintaining periodontal homeostasis and also ...participated in orthodontic tooth movement (OTM). Various studies have applied controlled mechanical stimulation to PDLSCs and investigated the effects of orthodontic force on PDLSCs. Physical stimuli can regulate the proliferation and differentiation of PDLSCs. During the past decade, a variety of studies has demonstrated that applied forces can activate different signaling pathways in PDLSCs, including MAPK, TGF-β/Smad, and Wnt/β-catenin pathways. Besides, recent advances have highlighted the critical role of orthodontic force in PDLSC fate through mediators, such as IL-11, CTHRC1, miR-21, and H2S. This perspective review critically discusses the PDLSC fate to physical force in vitro and orthodontic force in vivo, as well as the underlying molecular mechanism involved in OTM.
The evolutionarily conserved Piezo proteins, including Piezo1 and Piezo2, constitute a bona fide class of mechanosensitive (MS) cation channels, which play critical roles in various mammalian ...physiologies, including sensation of touch, proprioception and regulation of vascular development, and blood pressure. Furthermore, mutations in Piezos have been linked to various human genetic diseases, validating their potential as therapeutic targets. Thus, it is pivotal to understand how Piezo channels effectively convert mechanical force into selective cation permeation, and therefore precisely control the various mechanotransduction processes. On the basis of our recently determined cryoelectron microscopy structures of the full‐length 2547‐residue mouse Piezo1, structure‐guided mutagenesis, and electrophysiological and pharmacological characterizations, here we focus on reviewing the key structural features and functional components that enable Piezo1 to employ a lever‐like mechanogating mechanism to function as a sophisticated mechanotransduction channel.
The mechanosensitive Piezo1 channel possesses a 38‐TM topology model and forms a unique three‐bladed, propeller‐like structure comprising three structural and functional modules: the TM‐blade‐constituted mechanosensing module that consists of nine repetitive transmembrane helical units (THUs), the C‐terminal ion‐conducting pore module, and the transduction module including the beam, anchor, and CTD. The THU‐beam‐structure constitutes a lever‐like transduction pathway for long‐distance chemical‐ and mechanical gating of Piezo1.
Mountainous evidence suggests that inflammation, cardiomyocyte apoptosis and pyroptosis are involved in the development of sepsis and sepsis-induced cardiomyopathy (SIC). Stimulator of interferon ...genes (STING) is an indispensable molecule that could regulate inflammation and immune response in multiple diseases. However, the role of STING in cardiovascular disease, especially SIC remains unclear. This study was designed to investigate the potential molecular mechanisms of STING in lipopolysaccharide (LPS)-induced cardiac injury using STING global knockout mice. In wild type mice and cardiomyocytes, LPS stimulation triggered the perinuclear translocation of STING, which further bound to Type-I interferons (IFN) regulatory factor 3 (IRF3) and phosphorylated IRF3. Phosphorylated (P-) IRF3 subsequently translocated into nucleus and increased the expression of NOD-like receptor protein 3 (NLRP3). Knockout of STING in mice significantly improved survival rate and cardiac function, apart from suppressing myocardial and serum inflammatory cytokines, apoptosis, as well as cardiomyocyte pyroptosis. In vitro experiments revealed that NLRP3 overexpression by adenovirus could offset protective effects of STING knockdown in LPS-induced cardiomyocytes. Additionally, LPS stimulation also promoted the production of intracellular reactive oxygen (ROS), which further induced the NLRP3 translocation to the cytoplasm from the nucleus. Dissociative TXNIP could directly interact with cytoplasmic NLRP3 and form inflammasome, eventually triggering cardiomyocyte injury. Collectively, our findings disclose that STING deficiency could alleviate LPS-induced SIC in mice. Hence, targeting STING in cardiomyocytes may be a promising therapeutic strategy for preventing SIC.
The red blood cell distribution width (RDW) obtained from a standard complete blood count (CBC) is a convenient and inexpensive biochemical parameter representing the variability in size of ...circulating erythrocytes. Over the past few decades, RDW with mean corpuscular volume (MCV) has been used to identify quite a few hematological system diseases including iron-deficiency anemia and bone marrow dysfunction. In recent years, many clinical studies have proved that the alterations of RDW levels may be associated with the incidence and prognosis in many cardiovascular and cerebrovascular diseases (CVDs). Therefore, early detection and intervention in time of these vascular diseases is critical for delaying their progression. RDW as a new predictive marker and an independent risk factor plays a significant role in assessing the severity and progression of CVDs. However, the mechanisms of the association between RDW and the prognosis of CVDs remain unclear. In this review, we will provide an overview of the representative literatures concerning hypothetical and potential epidemiological associations between RDW and CVDs and discuss the underlying mechanisms.
The host immune response to bone biomaterials is vital in determining scaffold fates and bone regeneration outcomes. The nanometer-scale interface of biomaterials, which independently controls ...physical inputs to cells, regulates osteogenic differentiation of stem cells and local immune response. Herein, we fabricated biomimetic hierarchical intrafibrillarly mineralized collagen (HIMC) with a bone-like staggered nanointerface and investigated its immunomodulatory properties and mesenchymal stem cell (MSC) recruitment during endogenous bone regeneration. The acquired HIMC potently induced neo-bone formation by promoting CD68+CD163+ M2 macrophage polarization and CD146+STRO-1+ host MSC recruitment in critical-sized bone defects. Mechanistically, HIMC facilitated M2 macrophage polarization and interleukin (IL)-4 secretion to promote MSC osteogenic differentiation. An anti-IL4 neutralizing antibody significantly reduced M2 macrophage-mediated osteogenic differentiation of MSCs. Moreover, HIMC-loaded-IL-4 implantation into critical-sized mandible defects dramatically enhanced bone regeneration and CD68+CD163+ M2 macrophage polarization. The depletion of monocyte/macrophages by clodronate liposomes significantly impaired bone regeneration by HIMC, but did not affect MSC recruitment. Thus, in emulating natural design, the hierarchical nanointerface possesses the capacity to recruit host MSCs and promote endogenous bone regeneration by immunomodulation of macrophage polarization through IL-4.
The explosive demands of storage capacity and the von Neumann bottleneck of modern computer architectures trigger many innovations in information technology. Amongst them, nonvolatile spintronics ...attract considerable attentions for which can embed the computation capability into memory, enable neuromorphic, and probabilistic computing. These exciting progresses typically rely on the manipulation of the relative magnetization orientations of two magnetic layers. By extending to 3D spintronic architectures made of multiple magnetic layers (n), the exponentially increased 2n magnetic states can provide ample opportunities for implementing novel spintronic functionalities. Here, through building perpendicularly magnetized 3D spin‐orbitronic architectures – Pt/Fe1−xTbx/Si3N4n multilayers, it is demonstrated the electrical programing of 2n memory states via current‐induced spin–orbit torques (SOTs), and the accompanied reconfigurable multifunction in‐memory logic features in a single four‐terminal Hall device. Further, an electrical readout of these 2n states, together with the implementation of Boolean logic gates and digital circuitry such as 2–4 and 3–8 decoders, are successfully conducted. More complex logic circuits are also envisioned. The experiments thus substantiate 3D spin‐orbitronic structures as a promising platform for exponentially boosting the storage capacity and accommodating in‐memory computing that can be important for promoting the emerging 3D nanospintronics.
In a single 3D spin‐orbitronic cell made of Pt/Fe1−xTbx/Si3N4n multilayer, the electrical programing of 2n memory states via current‐induced spin–orbit torques, and the accompanied reconfigurable multifunction in‐memory logic features are demonstrated.
Objectives
Mechanical force plays an important role in modulating stem cell fate and behaviours. However, how periodontal ligament stem cells (PDLSCs) perceive mechanical stimulus and transfer it ...into biological signals, and thereby promote alveolar bone remodelling, is unclear.
Materials and Methods
An animal model of force‐induced tooth movement and a compressive force in vitro was used. After force application, tooth movement distance, mesenchymal stem cell and osteoclast number, and proinflammatory cytokine expression were detected in periodontal tissues. Then, rat primary PDLSCs with or without force loading were isolated, and their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation and immunoregulatory properties were evaluated. Under compressive force in vitro, the effects of the ERK signalling pathway on PDLSC characteristics were evaluated by Western blotting.
Results
Mechanical force in vivo induced PDLSC proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation; the force‐stimulated PDLSCs showed greater clonogenicity and proliferation, reduced differentiation ability, improved induction of macrophage migration, osteoclast differentiation and proinflammatory factor expression. The biological changes induced by mechanical force could be partially suppressed by TRPV4 inhibition. Mechanistically, force‐induced activation of TRPV4 in PDLSCs regulated osteoclast differentiation by affecting the RANKL/OPG system via ERK signalling.
Conclusions
Taken together, we show here that TRPV4 activation in PDLSCs under mechanical force contributes to changing their stem cell characteristics and modulates bone remodelling during tooth movement.
Mechanical force in vivo induced periodontal ligament stem cell proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation. The activation of TRPV4 in PDLSCs under mechanical force contributes to the changes in their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation, and immunoregulation and modulates bone remodelling during tooth movement.
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