UBE2C orchestrates bone formation through stabilization of SMAD1/5.

While previous studies have demonstrated the role of ubiquitin-conjugating enzyme 2C (UBE2C) in promoting β-cell proliferation and cancer cell lineage expansion, its specific function and mechanism in bone marrow mesenchymal stem/stromal cells (BMSCs) growth and differentiation remain poorly understood. Our findings indicate that mice with conditional Ube2c deletions in BMSCs and osteoblasts exhibit reduced skeletal bone mass and impaired bone repair. A significant reduction in the proliferative capacity of BMSCs was observed in conditional Ube2c knockout mice, with no effect on apoptosis.

Mgp High-Expressing MSCs Orchestrate the Osteoimmune Microenvironment of Collagen/Nanohydroxyapatite-Mediated Bone Regeneration.

Activating autologous stem cells after the implantation of biomaterials is an important process to initiate bone regeneration. Although several studies have demonstrated the mechanism of biomaterial-mediated bone regeneration, a comprehensive single-cell level transcriptomic map revealing the influence of biomaterials on regulating the temporal and spatial expression patterns of mesenchymal stem cells (MSCs) is still lacking. Herein, the osteoimmune microenvironment is depicted around the classical collagen/nanohydroxyapatite-based bone repair materials via combining analysis of single-cell RNA sequencing and spatial transcriptomics.

Establishment of a 3D esthetic analysis workflow on 3D virtual patient and preliminary evaluation.

Background: In esthetic dentistry, a thorough esthetic analysis holds significant role in both diagnosing diseases and designing treatment plans. This study established a 3D esthetic analysis workflow based on 3D facial and dental models, and aimed to provide an imperative foundation for the artificial intelligent 3D analysis in future esthetic dentistry.

Methods: The established 3D esthetic analysis workflow includes the following steps: 1) key point detection, 2) coordinate system redetermination and 3) esthetic parameter calculation.

A balance of biocompatibility and antibacterial capability of 3D printed PEEK implants with natural totarol coating.

Objective: Polyetheretherketone (PEEK), a biomaterial with appropriate bone-like mechanical properties and excellent biocompatibility, is widely applied in cranio-maxillofacial and dental applications. However, the lack of antibacterial effect is an essential drawback of PEEK material and might lead to infection and osseointegration issues. This study aims to apply a natural antibacterial agent, totarol coating onto the 3D printed PEEK surface and find an optimized concentration with balanced cytocompatibility, osteogenesis, and antibacterial capability.

Alkaline shear-thinning micro-nanocomposite hydrogels initiate endogenous TGFβ signaling for in situ bone regeneration.

Recruiting endogenous stem cells to bone defects without stem cell transplantation and exogenous factor delivery represents a promising strategy for bone regeneration. Herein, we develop an alkaline shear-thinning micro-nanocomposite hydrogel (10-MmN), aiming to alkaline-activate endogenous TGFβ1 and achieve in situ bone regeneration. It contains polyethyleneimine (PEI)-modified gelatin, laponite nanoplatelets (LAP), a bicarbonate buffer with a pH of 10, and gelatin microspheres (MSs).

Apoptotic vesicles derived from human red blood cells promote bone regeneration via carbonic anhydrase 1.

Apoptotic vesicles (apoVs) are nanoscale vesicles derived from billions of apoptotic cells involved in the maintenance of the human body's homeostasis. Previous researches have shown that some apoVs, such as those derived from mesenchymal stem cells, contribute to bone formation. However, those apoVs cannot be extracted from patients in large quantities, and cell expansion is needed before apoV isolation, which limits their clinical translation.

BHLHE40 Maintains the Stemness of PαS Cells In Vitro by Targeting through the Wnt/β-Catenin Signaling Pathway.

Primary bone mesenchymal stem cells (BMSCs) gradually lose stemness during in vitro expansion, which significantly affects the cell therapeutic effects. Here, we chose murine PαS (SCA-1PDGFRαCD45TER119) cells as representative of BMSCs and aimed to explore the premium culture conditions for PαS cells. Freshly isolated (fresh) PαS cells were obtained from the limbs of C57/6N mice by fluorescence-activated cell sorting (FACS).

Organoid Culture Development for Skeletal Systems.

Organoids are widely considered to be ideal models that have been widely applied in many fields, including regenerative medicine, disease research and drug screening. It is distinguished from other three-dimensional culture model systems by self-organization and sustainability in long-term culture. The three core components of organoid culture are cells, exogenous factors, and culture matrix.

Characterization of mesenchymal stem cells in human fetal bone marrow by single-cell transcriptomic and functional analysis.

Bone marrow mesenchymal stromal/stem cells (MSCs) are a heterogeneous population that can self-renew and generate stroma, cartilage, fat, and bone. Although a significant progress has been made toward recognizing about the phenotypic characteristics of MSCs, the true identity and properties of MSCs in bone marrow remain unclear. Here, we report the expression landscape of human fetal BM nucleated cells (BMNCs) based on the single-cell transcriptomic analysis.

A dual-responsive polydopamine-modified hydroxybutyl chitosan hydrogel for sequential regulation of bone regeneration.

Delayed inflammatory reaction and poor osteogenesis are the two main causes of failure for bone-defect healing. Accordingly, in the present study, a dual-responsive hydrogel composite was successfully fabricated in which near-infrared (NIR)-light-responsive polydopamine-coated magnesium-calcium carbonate microspheres are incorporated into a thermo-responsive hydroxybutyl chitosan hydrogel to provide sequential delivery of the anti-inflammatory drug aspirin and osteogenic bone morphogenetic protein 2 (BMP-2). By initially releasing aspirin rapidly, the hydrogel composite efficiently ameliorates early-stage inflammatory reaction and promotes transition to the regenerative phase.

The PCK2-glycolysis axis assists three-dimensional-stiffness maintaining stem cell osteogenesis.

Understanding mechanisms underlying the heterogeneity of multipotent stem cells offers invaluable insights into biogenesis and tissue development. Extracellular matrix (ECM) stiffness has been acknowledged as a crucial factor regulating stem cell fate. However, how cells sense stiffness cues and adapt their metabolism activity is still unknown.

Mixed Reality and Haptic-Based Dental Simulator for Tooth Preparation: Research, Development, and Preliminary Evaluation.

Background: Virtual reality (VR) dental simulators are currently used in preclinical skills training. However, with the development of extended reality technologies, the use of mixed reality (MR) has shown significant advantages over VR.

Objective: This study aimed to describe the research and development of a newly developed MR and haptic-based dental simulator for tooth preparation and to conduct a preliminary evaluation of its face validity.

Interdisciplinary 3D digital treatment simulation before complex esthetic rehabilitation of orthodontic, orthognathic and prosthetic treatment: workflow establishment and primary evaluation.

Background: An interdisciplinary treatment simulation and smile design before a complex esthetic rehabilitation is important for clinicians' decision-making and patient motivation. Meanwhile, intervention and interaction are necessary for dental specialists in these complex rehabilitations. However, it is difficult to visualize an interdisciplinary treatment plan by using the conventional method, especially when orthognathic surgery is involved, thus hindering communication between dental specialists.

CDC20 promotes bone formation via APC/C dependent ubiquitination and degradation of p65.

The E3 ubiquitin ligase complex CDC20-activated anaphase-promoting complex/Cyclosome (APC/C ) plays a critical role in governing mitotic progression by targeting key cell cycle regulators for degradation. Cell division cycle protein 20 homolog (CDC20), the co-activator of APC/C, is required for full ubiquitin ligase activity. In addition to its well-known cell cycle-related functions, we demonstrate that CDC20 plays an essential role in osteogenic commitment of bone marrow mesenchymal stromal/stem cells (BMSCs).

A NOTCH1/LSD1/BMP2 co-regulatory network mediated by miR-137 negatively regulates osteogenesis of human adipose-derived stem cells.

Background: MicroRNAs have been recognized as critical regulators for the osteoblastic lineage differentiation of human adipose-derived stem cells (hASCs). Previously, we have displayed that silencing of miR-137 enhances the osteoblastic differentiation potential of hASCs partly through the coordination of lysine-specific histone demethylase 1 (LSD1), bone morphogenetic protein 2 (BMP2), and mothers against decapentaplegic homolog 4 (SMAD4). However, still numerous molecules involved in the osteogenic regulation of miR-137 remain unknown.

DUSP5 promotes osteogenic differentiation through SCP1/2-dependent phosphorylation of SMAD1.

Dual-specificity phosphatases (DUSPs) are defined by their capability to dephosphorylate both phosphoserine/phosphothreonine (pSer/pThr) and phosphotyrosine (pTyr). DUSP5, a member of DUSPs superfamily, is located in the nucleus and plays crucially regulatory roles in the signaling pathway transduction. In our present study, we discover that DUSP5 significantly promotes osteogenic differentiation of mesenchymal stromal cells (MSCs) by activating SMAD1 signaling pathway.

The Current Situation and Future Prospects of Simulators in Dental Education.

The application of virtual reality has become increasingly extensive as this technology has developed. In dental education, virtual reality is mainly used to assist or replace traditional methods of teaching clinical skills in preclinical training for several subjects, such as endodontics, prosthodontics, periodontics, implantology, and dental surgery. The application of dental simulators in teaching can make up for the deficiency of traditional teaching methods and reduce the teaching burden, improving convenience for both teachers and students.

Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis.

Osteoporosis is a systemic metabolic bone disease with characteristics of bone loss and microstructural degeneration. The personal and societal costs of osteoporosis are increasing year by year as the ageing of population, posing challenges to public health care. Homing disorders, impaired capability of osteogenic differentiation, senescence of mesenchymal stem cells (MSCs), an imbalanced microenvironment, and disordered immunoregulation play important roles during the pathogenesis of osteoporosis.

NIR light-assisted phototherapies for bone-related diseases and bone tissue regeneration: A systematic review.

Recently, the rapid development of biomaterials has induced great interest in the precisely targeted treatment of bone-related diseases, including bone cancers, infections, and inflammation. Realizing noninvasive therapeutic effects, as well as improving bone tissue regeneration, is essential for the success of bone‑related disease therapies. In recent years, researchers have focused on the development of stimuli-responsive strategies to treat bone-related diseases and to realize bone regeneration.

UNC-5 netrin receptor B regulates adipogenesis of human adipose-derived stem cells through JNK pathway.

Background: There is a balance between adipogenic differentiation and osteogenic differentiation of human adipose-derived stem cells (hASCs). It is essential to explore the mechanism of hASCs lineage commitment. In our previous study, UNC-5 netrin receptor B (UNC5B) was identified as a positive regulator for osteogenesis.

Preliminary Clinical Application of Complete Workflow of Digitally Designed and Manufactured Sports Mouthguards.

Purpose: To establish a complete digital workflow for the design and manufacture of sports mouthguards and to observe preliminary clinical effects.

Materials And Methods: Eighteen healthy participants were included in this study. The self-controlled method was applied, and all participants were provided with two types of mouthguards.

Four-dimensional bioprinting: Current developments and applications in bone tissue engineering.

Four-dimensional (4D) bioprinting, in which the concept of time is integrated with three-dimensional (3D) bioprinting as the fourth dimension, has currently emerged as the next-generation solution of tissue engineering as it presents the possibility of constructing complex, functional structures. 4D bioprinting can be used to fabricate dynamic 3D-patterned biological architectures that will change their shapes under various stimuli by employing stimuli-responsive materials. The functional transformation and maturation of printed cell-laden constructs over time are also regarded as 4D bioprinting, providing unprecedented potential for bone tissue engineering.

Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1-Dependent Autophagy.

Mitochondrial phosphoenolpyruvate carboxykinase (PCK2) is a rate-limiting enzyme that plays critical roles in multiple physiological processes. The decompensation of PCK2 leads to various energy metabolic disorders. However, little is known regarding the effects of PCK2 on osteogenesis by human mesenchymal stem cells (hMSCs).

Extracellular vesicles as a novel therapeutic tool for cell-free regenerative medicine in oral rehabilitation.

Oral maxillofacial defects may always lead to complicated hard and soft tissue loss, including bone, nerve, blood vessels, teeth and skin, which are difficult to restore and severely influence the life quality of patients. Extracellular vesicles (EVs), including exosomes, microvesicles and apoptotic bodies, are emerging as potential solutions for complex tissue regeneration through cell-free therapies. In this review, we highlight the functional roles of EVs in the regenerative medicine for oral maxillofacial rehabilitation, specifically bone, skin, blood vessels, peripheral nerve and tooth-related tissue regeneration.