Search Results (1,086)

Unloading-induced bone loss is a major medical challenge during long-duration human spaceflight, largely driven by suppressed osteoblast-mediated bone formation, and practical countermeasures are needed. Electromagnetic stimulation has shown benefits for bone repair, and its non-invasiveness supports potential space use; however, its single-modality efficacy remains limited. Here, we investigated a combined electromagnetic field (CEMF) integrating a static magnetic field (SMF, 0.4–0.6 T) and a pulsed electromagnetic field (PEMF, 0.38 ± 0.19 mT) to attenuate unloading-related bone loss and examine field-induced mechanical stimulation. Finite-element simulations mapped magnetic flux density, field gradient, induced current density, and Lorentz force density in bone tissue. CEMF was evaluated in vivo in hindlimb unloading (HLU) mice and in vitro in MC3T3-E1 osteoblasts. CEMF improved bone mineral density, trabecular and cortical microarchitecture, and mechanical properties in HLU mice, with increased osteoblast number and mineral apposition rate. In vitro, CEMF promoted osteogenic differentiation and upregulated COL1A1 and RUNX2. Transcriptome analysis suggested activation of ECM–integrin mechanical signaling and the PI3K–AKT pathway. These findings indicate that CEMF-induced multiphysics stimulation enhances osteogenic responses and may serve as a complementary, non-invasive countermeasure for spaceflight-associated bone loss. Full article

In equine veterinary medicine, there is a lack of correlation between the structural severity of orthopaedic disease and the perceived severity of presenting signs, resulting in a variable influence on performance, pain and disability. Across equine industries, there is selective pressure through breeding for specific traits, such as the “speed” gene (MSTN) in racing thoroughbreds and the “gait keeper” gene (DMTR3) in pacing breeds, potentially resulting in genetic predispositions that lead to an increased risk of musculoskeletal disorders. With advancements in molecular sequencing techniques, researchers have been able to identify various genes (e.g., ECA, RUNX, and ADAME1) as well as biomarkers influencing performance and the development of orthopaedic disease. In combination, these techniques could be applied clinically in the future to improve welfare and disease management through advanced characterization and treatments to delay the onset of orthopaedic disease. Full article

Aberrant expression of multiple microRNAs has been reported in gastric cancer. In particular, microRNA-597 has been associated with poor survival rates but is not yet well characterized. Seventy-five clinical samples, four cell lines, and two patient-derived organoids were evaluated for the expression of microRNA-597 and its target genes. microRNA-597 was transiently transfected for analysis of cell migration, invasion, wound healing, colony formation, and cell viability, and its regulation by long non-coding RNAs was explored using the TCGA-STAD and LncBook tools. In clinical samples, low expression of microRNA-597 was associated with the intestinal subtype (p = 0.002) and stages III and IV (p = 0.048). All functional readouts were reduced after microRNA-597 transfection, including colony formation, in patient-derived organoids. Among target genes, RUNX1 was directly regulated by microRNA-597. Other cell invasion genes were dependent on RUNX1 as a hub for regulation. Analysis of the Intersection between long non-coding RNAs co-expressed with RUNX1 and those with the highest microRNA-597 prediction binding identified KCNQ1OT1 as the top transcript. Silencing of KCNQ1OT1 and co-expression in clinical samples suggest the existence of a KCNQ1OT1/microRNA-597/RUNX1 network. The results indicate that microRNA-597 directly suppresses RUNX1, while KCNQ1OT1 modulates this interaction. Our approach enabled the simultaneous analysis of dysregulation in three families of transcripts in gastric cancer progression. Full article

The prevalent endocrine disruptor bisphenol A (BPA) is associated with aging-related conditions, including metabolic disorders. It has been shown that BPA promotes bone fragility through oxidative stress-induced apoptosis and impaired osteoblast differentiation. The identification of sustainable bioactive substances that alleviate BPA-induced bone toxicity is thus of biomedical and environmental significance. Wolffia globosa (WG), the world’s smallest flowering aquatic plant, has recently gained attention as a high-protein, antioxidant-rich nutraceutical, yet its impact on BPA-induced osteoblast dysfunction has not been systematically investigated. This study presents a comprehensive assessment of WG ethanolic extract (WGE) in MC3T3-E1 pre-osteoblasts, incorporating thorough phytochemical characterization, acute high-dose and chronic low-dose BPA exposure models, and multi-faceted mechanistic analysis. LC-MS/MS profiling identified luteolin (116.17 ± 0.69 µg/g), rosmarinic acid (54.80 ± 2.12 µg/g), and apigenin (48.77 ± 0.61 µg/g) as the predominant bioactive compounds. WGE exhibited potent antioxidant capacity across DPPH and ABTS radical scavenging assays, complemented by high ORAC and FRAP values, reflecting broad-spectrum antioxidant mechanisms. Treatment with WGE (25 and 50 µg/mL) resulted in significant alleviation of BPA-induced cytotoxicity, decreased intracellular ROS levels, and inhibited apoptosis. WGE (12.5 µg/mL) also modulated autophagy-related markers (LC3-II, Beclin-1, and p62), suggesting potential autophagic participation, although flux verification was not conducted. Treatment with WGE (12.5 µg/mL) also restored BPA-suppressed osteogenesis under chronic exposure, as evidenced by enhanced alkaline phosphatase activity, and increased both mineralization and upregulation of osteogenic genes including runt-related transcription factor2 (Runx2), collagen type I alpha 1 (Colla1), alkaline phosphatase (ALP), and osteocalcin (OCN). These effects were accompanied by partial reactivation of Wnt/β-catenin signaling. This study is the first to demonstrate that WGE protects osteoblasts from BPA toxicity by concurrently strengthening antioxidant defenses, limiting apoptosis, modulating autophagy-related markers, and supporting β-catenin-mediated osteogenesis, highlighting WG as a promising sustainable nutraceutical candidate for the prevention of environmental toxin-related bone fragility. Full article

Medication-related osteonecrosis of the jaw (MRONJ) is a complex condition associated with the use of antiresorptive drugs, such as bisphosphonates and denosumab. The condition is characterized by the presence of exposed bone in the maxillofacial region that fails to heal. MRONJ remains highly intractable, as its pathogenic mechanisms are not yet fully understood. It is therefore essential to elucidate the molecular mechanisms underlying the disease. MiRNA expression analysis and proteomic studies were performed on a selected cohort of patients with MRONJ on jawbone tissue, using qRT-PCR and 2D electrophoresis followed by mass spectrometry. MiRNAs and proteomics data validation was carried out by Western blot analysis of differentially expressed proteins highlighted by a proteome study and predicted targets of differentially expressed miRNAs. Nineteen miRNAs were overexpressed and two downregulated in jawbone tissue from all MRONJ patients. Notably, five of these dysregulated miRNAs are involved in the regulation of angiogenesis and desmosome functions, suggesting a potential link to the molecular alterations observed at the protein level. Proteomic analysis revealed decreased concentrations of the pigment epithelium-derived factor, and of desmoglein-1, a desmosomal cadherin. Validation analysis confirmed the dysregulation of pathways involved in bone remodeling and necroptosis. The pathophysiology of MRONJ arises from a complex interplay of factors, including impaired bone remodeling, affected angiogenesis, and altered cell adhesion and differentiation mechanisms, ultimately leading to necroptosis. Through proteomic analysis and validation of miRNA expression, our study proposes specific molecular alteration in MRONJ-compromised bone tissue, involving desmosomal component imbalance and angiogenesis inhibition. Full article

Background/Objectives: Chromosomal microarray analysis (CMA) is an essential tool in modern cytogenetics for detecting copy number alterations and copy-neutral loss of heterozygosity (CN-LOH). As optical genome mapping (OGM) emerges as a potential replacement for traditional cytogenetic methods, the extent to which CMA remains necessary in routine diagnostic workflows remains to be elucidated. Methods: We retrospectively reviewed 53 primary neoplastic cases, selected from a larger cohort of 327 hematologic malignancy specimens, in which CMA identified one or more CN-LOH events. Event size, genomic content, and correlation with next-generation sequencing (NGS) findings were assessed. A separate cohort of newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) was analyzed to evaluate disease-specific CN-LOH frequency. Results: Nearly half of CN-LOH events detected were <25 Mb, below the current detection threshold of OGM inferred from published benchmarks and validated workflows. Many encompassed clinically relevant genes, including FLT3, JAK2, TET2, TP53, and RUNX1. Additionally, two-thirds of cases harbored pathogenic or likely pathogenic variants by NGS within the corresponding CN-LOH regions, further underscoring the clinical value of detecting these copy-neutral events. In contrast, CN-LOH was uncommon in B-ALL, and most alterations identified by CMA would be detectable by OGM. Many of these patients also harbored complex structural rearrangements that required multiple conventional assays for full characterization; these could be resolved by OGM in a single analysis. Conclusions: Our findings indicate that although OGM excels at resolving complex structural variants, CMA remains essential for detecting copy-neutral events. Until OGM achieves improved sensitivity for CN-LOH, an integrated approach utilizing conventional cytogenetics, CMA, NGS, and OGM provides the most reliable framework for comprehensive genomic assessment across cancer types. Full article

Background/Objectives: Osteoporosis remains a clinically important metabolic bone disorder with limited bone-forming therapeutic options. SET domain bifurcated protein 1 (SETDB1) is involved in osteogenic epigenetic regulation, but small-molecule discovery guided by SETDB1-associated structural regions remains limited. This study aimed to identify a candidate compound with in silico relevance to a SETDB1-associated ligand-bound pocket and assess its association with early osteogenic readouts. Methods: A computational–experimental workflow was used, including hierarchical molecular docking, MM-GBSA rescoring, ADMET-based prioritization, redocking validation, molecular dynamics simulations, and preliminary in vitro evaluation in MC3T3-E1 cells. Compound 271 (C271) was selected based on structure-based screening results and predicted developability-related properties. Cytocompatibility, alkaline phosphatase (ALP) activity and staining, selected molecular markers, and SETDB1–H3 molecular dynamics behavior were evaluated. Results: Redocking reproduced the reference binding mode, and molecular dynamics simulations indicated that C271 maintained a relatively persistent conformation around the predicted SETDB1-associated pocket. Comparative SETDB1–H3 simulations showed altered H3 dynamics and SETDB1–H3 contact patterns in the C271-containing system. In cell-based assays, C271 showed no appreciable cytotoxicity within the tested concentration range and was associated with increased ALP activity and staining. C271 treatment was accompanied by higher global H3K9me3 and Runx2 levels, whereas SETDB1 protein abundance remained largely unchanged. Conclusions: C271 was identified as a computationally prioritized SETDB1-related candidate compound associated with early osteogenic-associated cellular responses. The evidence supports computational plausibility and cell-level association, but does not establish direct SETDB1 engagement, SETDB1 enzymatic modulation, SETDB1-dependent causality, or late-stage osteogenic maturation/mineralization. Given the single-compound evaluation, further target-engagement, enzymatic, and functional studies are needed. Full article

Objective: This systematic review aims to evaluate the effects of statin administration on orthodontic tooth movement (OTM) and post-treatment relapse in animal models. Materials and Methods: Following PRISMA guidelines and PROSPERO registration (CRD42025612449), a comprehensive literature search was performed in PubMed, Scopus, and the Cochrane Library up to December 2025. The search strategy included studies on animal models treated with any form of statin during OTM or relapse phases. Eligibility criteria were defined using the PICOS framework. Data extraction focused on study characteristics, statin administration protocol, orthodontic mechanics, and both histological and molecular markers of bone remodeling. Risk of bias was assessed with SYRCLE’s tool. Results: Seven in vivo animal studies met the inclusion criteria. Simvastatin and atorvastatin were investigated using heterogeneous experimental models, doses, administration routes, orthodontic mechanics, and follow-up periods. Findings suggested that statins may reduce active orthodontic tooth movement or post-orthodontic relapse in some experimental settings, but effects were not uniform across studies. Histological outcomes, when reported, generally indicated reduced osteoclast activity, fewer resorption lacunae, or more mature alveolar bone in statin-treated animals. Molecular outcomes were less consistently reported and mainly involved OPG/RANKL-related pathways, Runx2, or ALP expression. Conclusions: Statins, particularly simvastatin, show potential to modulate orthodontic tooth movement and reduce relapse by influencing bone metabolism. Nevertheless, due to methodological variability and the exclusive reliance on animal models, these results cannot yet be translated into clinical recommendations. Current preclinical evidence suggests that statins may modulate bone remodeling during active orthodontic tooth movement and after appliance removal. However, the evidence remains limited to a small number of heterogeneous animal studies with incomplete reporting of key outcomes and several unclear risk-of-bias domains. Clinical translation is premature, and more standardized preclinical studies are required before human investigations can be justified. Full article

Background: Yes-associated protein 1 (YAP1), a key effector of the Hippo signaling pathway and mechanosensitive transcriptional coactivator, plays a complex role in osteoarthritis (OA) and cartilage regeneration. While YAP1 is essential for tissue homeostasis, its dysregulation has been implicated in both inflammatory and degenerative joint pathologies. However, its precise function remains ambiguous. Methods: We silenced YAP1 with small interfering RNA (siYAP1) in two human-cell-based models relevant to OA pathogenesis and cartilage repair: (1) IL-1β (10 ng/mL)-stimulated articular chondrocytes in monolayer and pellet cultures, and (2) TGF-β1 (10 ng/mL)-induced chondrogenesis in MSC pellet cultures. Outcome measures comprised YAP1 nuclear localization; inflammatory/catabolic markers in chondrocytes (IL6, IL8, ADAMTS5, MMP13); and, in MSC pellets, chondrogenic or hypertrophic markers (COL2A1, ACAN, RUNX2, MMP13, COL10A1) together with glycosaminoglycan (GAG) deposition. Statistical significance was assessed using an ANOVA or Friedman test with post hoc correction (Tukey or Dunn’s test, respectively); p < 0.05 was considered significant. Results: In human chondrocytes, siYAP1 reduced IL-1β-induced nuclear YAP1 localization and suppressed pro-inflammatory mediators IL6 and IL8, indicating an anti-inflammatory effect. YAP1 silencing also downregulated ADAMTS5 expression in 2D monolayers but not in 3D pellet cultures, suggesting reduced regulatory influence in the three-dimensional environment. Notably, MMP13 expression was paradoxically increased following YAP1 knockdown, underscoring the complexity of YAP1’s role in catabolic regulation. In MSC chondrogenesis, siYAP1 enhanced TGF-β1-induced chondrogenesis by increasing COL2A1 and ACAN expression and promoting GAG deposition on day 21. Additionally, it reduced hypertrophic markers RUNX2 and MMP13 on day 7, though COL10A1 remained elevated compared to negative siRNA, indicating only partial suppression of hypertrophic differentiation. Nuclear YAP1 levels were increased by day 21 despite reduced mRNA, suggesting post-transcriptional regulation or enhanced nuclear translocation. Conclusions: These findings demonstrate that YAP1 knockdown exerts context-specific anti-inflammatory and pro-chondrogenic effects while partially mitigating hypertrophy. However, divergent outcomes, namely elevated MMP13 in chondrocytes and upregulated COL10A1 in MSCs, indicate that YAP1 silencing does not uniformly suppress inflammation or hypertrophy. YAP1 represents a potential therapeutic target for OA, but its modulation requires careful consideration of cellular context, siRNA delivery method, and timing to optimize outcomes for cartilage repair and joint preservation. Full article

Bone marrow-derived mesenchymal stem cells (BMSCs) maintain skeletal homeostasis by balancing adipogenic and osteogenic differentiation, yet clinically used drugs that bias this fate choice and their mechanisms remain incompletely defined. Here, we investigated whether dextromethorphan (DXM), a widely used antitussive, modulated lineage commitment in rat BMSCs and interrogated candidate upstream signaling modules. Rat BMSCs were induced with adipogenic medium or osteogenic medium in the presence of DXM (30 μM). Adipogenesis and osteogenesis were quantified using Oil Red O and Alizarin Red S staining with elution-based quantification, and lineage markers were measured by RT-qPCR. Intracellular Ca²⁺ and ROS were analyzed using flow cytometry, and the levels of p-AKT and p-ERK were assessed through Western blotting analysis. Under adipogenic induction, DXM increased lipid droplet accumulation and the mRNA levels of Pparγ and Fabp4. Although DXM elevated Ca²⁺ and ROS, the chelation of intracellular Ca²⁺ and pharmacological inhibition of Sig-1R/PLC–IP3R signaling, redox/ROS, NMDA receptors, AKT/ERK, Kv channels, bitter taste receptor-related signaling, and mTOR did not attenuate the DXM-enhanced adipogenesis. DXM reduced p-ERK without increasing p-AKT; U0126 lowered basal adipogenesis but did not block the DXM effect. Under osteogenic induction, DXM reduced matrix mineralization and downregulated Runx2 and Bglap mRNA levels, while Wwtr1 mRNA levels were not significantly changed. DXM also partially reversed the osteogenic induction-associated reduction in Mtor mRNA. Separately, under adipogenic induction, rapamycin attenuated baseline adipogenesis but did not prevent the additional lipid accumulation induced by DXM. Collectively, DXM shifted the osteogenic–adipogenic balance toward adipogenesis through a non-canonical mechanism. Full article

RUNX1 alterations contribute to pediatric myeloid malignancies through both germline predisposition syndromes and somatic leukemogenic events, but their clinical and biological significance in children remains incompletely defined. This retrospective single-center study evaluated six pediatric patients with myelodysplastic syndromes or acute leukemias harboring RUNX1 variants, integrating clinical, cytogenetic, and targeted next-generation sequencing data, with germline status confirmed using non-hematopoietic tissues. Three patients carried germline RUNX1 variants, characterized by antecedent cytopenias, dysplastic features, and increased treatment-related toxicity, including severe infections, persistent cytopenias, and transplant-related mortality. In contrast, somatic RUNX1 alterations were associated with overt high-risk disease, frequently accompanied by complex cytogenetics or monosomy 7, and demonstrated heterogeneous outcomes ranging from sustained remission to post-transplant relapse. Mixed-phenotype acute leukemia was observed in both groups. These findings support a model of RUNX1-driven leukemogenesis, in which germline and somatic alterations represent distinct yet interconnected trajectories, while highlighting the importance of distinguishing variant origin for risk stratification, donor selection, and therapeutic decision-making in pediatric myeloid malignancies. Given the small cohort size, the findings remain descriptive and require validation in larger prospective studies. Full article

Pancreatic tumors frequently exhibit calcification, suggesting potential osteogenic-related phenotypic plasticity. This study aimed to systematically evaluate whether pancreatic ductal adenocarcinoma (PDAC) cells acquire osteogenic-like features under induction conditions and to assess the associated phenotypic and molecular changes. PDAC cell lines and non-malignant pancreatic epithelial cells were subjected to osteogenic induction. Mineralization, alkaline phosphatase (ALP) activity, osteogenic marker expression, and malignant phenotypes were evaluated. RNA sequencing was performed at defined time points to characterize transcriptional changes. Pharmacological inhibition of MEK and siRNA-mediated knockdown of RUNX2 were applied to examine the involvement of MAPK–ERK signaling and downstream transcriptional regulation. Osteogenic induction led to calcium deposition and increased ALP activity in a subset of PDAC cell lines, accompanied by upregulation of osteogenic-associated markers, including RUNX2 and SPP1. Induced cells exhibited reduced migration, clonogenicity, invasion, and proliferation. Transcriptomic analysis revealed activation of osteogenesis-related and calcium-transport pathways, along with downregulation of cell cycle programs. MAPK–ERK signaling was activated during induction, and MEK inhibition attenuated RUNX2 and ALP expression as well as mineralization-associated changes. Furthermore, RUNX2 knockdown reduced ALP expression and mineralization levels, indicating its contribution to the osteogenic-like phenotype. PDAC cells can acquire osteogenic-like features under defined induction conditions, accompanied by coordinated transcriptional reprogramming and reduced malignant phenotypes. The observed mineralization-associated phenotypes may reflect a combination of active processes and passive calcium deposition. In addition, the MAPK–ERK–RUNX2 axis appears to be involved in this process, although it may reflect a broader adaptive or stress-associated reprogramming rather than lineage commitment. These findings provide insight into the potential relationship between tumor calcification and phenotypic plasticity in PDAC. Full article

The human liver is a polyploid organ, dominantly featured by a high proportion of binuclear polyploid hepatocytes. Our recent study demonstrates that decline of the abundance of binuclear hepatocytes (ABH) plays a critical role in contributing to Hepatocellular carcinoma (HCC) formation, involving the cytokinesis regulator Anillin. However, the relevance between liver stiffness and the acquired ABH attenuation remains unclear. In this study, we set a mechanical environment gel with different gradients to simulate different liver stiffness environments, combined with the paired paracancerous liver tissues from real-world patients with HCC who underwent radical surgery. A mechanosensitive Piezo1/RUNX2/Anillin axis was discovered. As observed, the decline of ABH in paracancerous liver tissues is a noteworthy measurable value for tumor formation, correlated with the extent of liver matrix stiffness and dismal phenotypes. A stiffened culture environment may promote quick polyploid attenuation of hepatocytes, accompanied by high expression of Piezo1, a critical mechanosensitive ion channel, and a consequential nuclear translocation of RUNX2. Importantly, RUNX2 functions as an upstream transcription factor of Anillin. Regulating Piezo1/RUNX2 or using Piezo1 agonist remarkably affected Anillin expression and hepatocyte polyploidy homeostasis. Thus, we propose that the Piezo1/RUNX2/Anillin axis transduces the microenvironment mechanical signal from liver stiffening and impairs hepatocyte polyploidy homeostasis in HCC formation. Full article

Introduction: platelet-rich fibrin (PRF) is a second-generation platelet concentrate which is known for promoting cell migration, tissue repair, angiogenesis and bone formation. In contrast, the specific effects of trauma-activated PRF on mesenchymal stromal cells (MSC) are not yet fully understood. The present study investigates systemic effects of surgical trauma-activated PRF on MSCs in vitro, analyzing their metabolic activity, inflammatory responses, and regenerative capacity to optimize advanced treatment concepts for severe fractures and injuries. Material & Methods: PRF membranes (T-PRF from trauma patients, C-PRF from healthy controls) were generated. After co-incubation with MSC cells for 24, 72, and 120 h, further investigations of metabolic activity (MTT assay) and gene expression analyses were performed. Results: for MTT assay, results especially showed a significantly higher metabolic activity of T-PRF after 120 h. ELISA-results measuring cytokine levels (CXCL10, IL-6, VEGF, and IDO) exposed a frequent peak in T-PRF group at 72 h, declining slightly at 120 h. In the gene expression analyses, T-PRF exerted a comparatively stronger stimulating effect on MAPK14 and VEGFA after 24 h, while a decrease in gene expression for MAPK8, MAPK14, and RUNX2 was observed over time. Conclusion: surgical trauma-activated PRF seems to be a powerful inducer of early inflammatory and stress responses in MSCs with preserved angiogenic but limited osteogenic signaling. Therefore, a targeted balance between inflammatory activation and sustainable regeneration, as well as optimized preparation and possible combination with immunomodulatory approaches, appear to be crucial for the therapeutic success of PRF-based strategies. Full article

Dental pulp tissue contains mesenchymal stem/progenitor cells that possess high proliferative potential for self-renewal. They are neural-crest derived cells and exhibit multi-lineage differentiation properties. These progenitor stem cells are now recognized as being vital to the dentin regeneration process following injury. Understanding the molecular mechanisms that mediate the differentiation of adult stem cells into odontoblasts and their use in the repair of the dentin–pulp complex is of significant interest in regenerative dental medicine. Dentin Phosphophoryn (DPP), synthesized and processed predominantly by the odontoblasts, functions both as a structural and signaling protein. We had previously demonstrated that DPP activates NF-κB and promotes Wnt5a expression in dental pulp stem cells. In this context, we observed that DPP can activate TAZ, a biologically potent transcriptional coactivator which serves as a downstream element of the NF-κB signaling cascade. Furthermore, binding of NF-κB p65 subunit to the TAZ promoter was facilitated by DPP stimulation, and their interaction was confirmed by ChIP analysis. In addition, DPP-dependent activation of the TAZ/TEAD reporter was confirmed by luciferase activity in DPSCs. Co-immunoprecipitation analysis confirmed the in vivo interaction between TAZ and β-catenin with DPP stimulation. This regulatory complex facilitated TAZ to bind to the conserved TEAD binding motifs of key gene targets involved in odontogenic differentiation such as RUNX2, OSX, OCN, ALP, BMP4, and WNT5A. Some of these genes also contain binding sites for the TCF/LEF transcription factors that interact with the Wnt effector, β-catenin. Activation of TAZ and β-catenin resulted in the upregulation of odontoblast gene expression and reduced expression in the presence of the TAZ–TEAD protein complex inhibitor. Using mandibles of DSPP KO and WT mice, we confirmed reduced TAZ and β-catenin protein levels in the dental pulp cells and in the odontoblasts of DSPP KO mice when compared with WT. Thus, DPP, an extracellular matrix protein, provides biological cues to activate the TAZ signaling pathway that can stimulate the terminal differentiation of DPSCs into functional odontoblasts. Full article