Frontiers in Cell and Developmental Biology最新文献

Temporomandibular disorders (TMDs) and end-stage osteoarthritis are among the most common disabling diseases of the oral and maxillofacial region. Due to its unique fibrocartilaginous structure and limited vascularization, the temporomandibular joint (TMJ) possesses an extremely limited intrinsic regenerative capacity. Unlike conventional treatments that predominantly address symptoms, autologous platelet-derived products (APDs), such as platelet-rich plasma, platelet-rich fibrin, and concentrated growth factors, have been increasingly investigated for their biological roles in TMJ repair by mimicking natural healing mechanisms. This review summarizes the technical evolution of APDs and elucidates the molecular mechanisms promoting TMJ regeneration. Specifically, it discusses how APDs modulate the TMJ microenvironment by driving mesenchymal stem cell proliferation, directing chondrogenic differentiation, and resolving inflammation through immunomodulatory cascades. In addition, this review discusses the relevance of rheological properties for stage-specific clinical application and outlines translational considerations for the use of APDs in the management of TMDs.

The interaction of actin filaments with the nuclear envelope is essential for diverse cellular processes, including cell migration, nuclear positioning, and transcriptional control. The main studied mechanism that links F-actin to the nucleus is the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex. Recently, the formation of a perinuclear actin rim has been identified in various cell types in response to external force or migration signals. This rim depends on the activation of the actin nucleator Inverted formin 2 (INF2) by calcium influx. However, it is unclear how the rim is coupled to the nuclear envelope. Here, we show that the nuclear membrane protein Emerin, which has an actin-binding domain, is not required for the perinuclear actin rim formation. Interestingly, we found that the Ezrin-Radixin-Moesin (ERM) proteins, known to link actin filaments to the cell membrane, are also localized to the nuclear envelope in melanoma cells. Knockdown of ERM proteins led to a reduction in the rim levels, while overexpression of ERM proteins increased the perinuclear actin rim levels. Overexpression of Ezrin also improved the rim formation in HeLa cells upon addition of a calcium ionophore. Thus, the ERM proteins appear to participate in a mechanism that links actin filaments to the nuclear envelope.

[This retracts the article DOI: 10.3389/fcell.2021.652939.].

[This corrects the article DOI: 10.3389/fcell.2025.1719544.].

Background: Gestational diabetes mellitus (GDM) has been linked to altered leptin (LEP) gene methylation, which may disrupt maternal glucose metabolism and the associated placental signaling. However, the changes of LEP methylation involved in GDM pathophysiology throughout pregnancy remain unclear.

Methods: Female C57BL/6J mice (6-8 weeks old) were randomly divided into control and GDM groups (n = 40 each). The GDM group was fed a high-fat diet for 4 weeks before mating and given a single streptozotocin injection (120 mg/kg, intraperitoneal injection) on gestational day 2, while controls received standard chow and citrate buffer. Fasting blood glucose and body weight were recorded at baseline, gestational days 5, 12, and 18, and postpartum day 1. Oral glucose tolerance tests (OGTTs) were performed at corresponding stages. Blood was collected for measurement of serum leptin concentrations by ELISA. Leptin protein expression and LEP promoter methylation in decidual tissues were analyzed by Western blot and bisulfite pyrosequencing, respectively. Weighted least-squares regression was used to evaluate the associations between leptin, LEP promoter methylation, and glucose metabolism.

Results: The high-fat diet and streptozotocin (HFD + STZ) combination successfully induced a GDM phenotype, as evidenced by early and persistent hyperglycemia and impaired glucose tolerance. Serum leptin levels were significantly increased in GDM mice before pregnancy and returned to the levels of pre-pregnancy in postpartum, indicating that the decidua plays an important role in the dynamic regulation of leptin during pregnancy. Western blot analysis confirmed higher leptin expression in the decidual tissue of GDM mice, while bisulfite pyrosequencing revealed significant demethylation of the LEP promoter. WLS analysis showed that leptin upregulation in GDM was closely associated with epigenetic remodeling at specific CpG sites within the LEP promoter, whereas the relationship between promoter demethylation and FBG was altered in GDM.

Conclusion: Decidual LEP promoter demethylation is associated with hyperleptinemia and shows an epigenetic mechanism linking GDM. LEP promoter demethylation may reflect the metabolic disturbance in GDM and serve as a potential early marker for GDM.

Introduction: Extended exposure to microgravity, such as experienced during spaceflight, significantly alters the mechanical environment of skeletal tissues, impacting cartilage development and function. Mechanical unloading disrupts the balance of cellular signaling and extracellular matrix synthesis in cartilage precursor cells, but the molecular consequences and temporal dynamics of these alterations remain incompletely understood.

Methods: We employed simulated microgravity via a random positioning machine (RPM) to investigate stage-specific transcriptomic and phenotypic responses in chondrogenic micromass cultures derived from embryonic chicken (Gallus gallus) limb bud cells. RNA sequencing, bioinformatic pathway analysis, and protein interaction network construction were performed on cultures exposed to microgravity for early (days 0-3), late (days 3-6), and continuous (days 0-6) periods.

Results: Continuous microgravity exposure resulted in robust differential expression of 648 genes (adjusted p-value <0.05, |log2 fold change| > 1), including suppression of canonical chondrogenic markers (SOX9, COL2A1) and upregulation of catabolic enzymes (MMP13, ADAMTS family). The affected key signaling pathways included disrupted TGF-β/BMP balance, Wnt/β-catenin activation, and cytoskeletal remodeling. Early and late exposures showed consistent gene expression trends but fewer statistically significant changes. Notably, adrenergic beta receptor 1 (ADRB1) was consistently upregulated across all time points.

Discussion: These findings demonstrate that simulated microgravity rapidly induces reversible molecular and cellular adaptations related to cartilage homeostasis and mechanotransduction in this chondrogenic model system. The RPM platform offers a powerful tool to dissect chondrogenesis, cartilage biology, and lineage plasticity under mechanical unloading, providing insights with broad relevance to skeletal tissue mechanobiology.

Chronic low-grade inflammation (metaflammation) constitutes a shared pathological nexus in obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD). While current therapies primarily alleviate metabolic symptoms, they often neglect underlying immune dysregulation orchestrated by nuclear receptors (NRs). This review proposes immune-centric pharmacology, a paradigm directly targeting immunocytes (e.g., macrophages, T cells) through spatiotemporal modulation of NR-mediated immunometabolic crosstalk (e.g., PPARγ/δ, FXR, LXRs) to disrupt inflammation-perpetuating microenvironments. We emphasized NRs as main regulatory factors of immunophenotypic reprogramming, spanning the interactions of fat, liver, and intestinal immunity, and comprehensively summarized the multicellular structure of "inflamed nexus." We gradually expand our discussion from the following three aspects: immune reprogramming targeting nr by novel biological agents (for example, TREM2 agonists activating PPARγ); advanced transmission systems enable tissue-specific NR regulation.; and the immunomodulatory mechanism of metabolic drugs utilizing the NR-immune axis. Current findings indicate that focused immunomodulation achieves via NR-guided immune-centric pharmacology represents a transformative framework for next-generation metabolic disease management, bridging pharmacological innovation with therapeutic translation.

Arthritis, a group of common diseases characterized by joint inflammation, cartilage destruction, and imbalance in bone remodeling, has high global prevalence and disability rates. In recent years, oxidative stress and chronic inflammation have been widely recognized as core mechanisms jointly driving its pathological process. The antioxidant response axis formed by nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) plays a key role in maintaining joint tissue redox balance and suppressing excessive inflammatory responses. Extensive basic and translational research indicates that the Nrf2/HO-1 pathway exerts protective effects through multiple mechanisms: reducing reactive oxygen species (ROS) levels, inhibiting nuclear factor-kappa B (NF-κB)-mediated inflammation, regulating macrophage polarization, and influencing processes such as apoptosis, ferroptosis, and fibrosis, thereby significantly alleviating tissue damage and clinical symptoms in arthritis. Currently, various natural products, small-molecule compounds, and drug repurposing strategies targeting the activation or regulation of this pathway have shown promising joint protective effects in animal experiments, suggesting Nrf2/HO-1 is a potential disease-modifying therapeutic target. This review systematically summarizes the latest research progress on the role of Nrf2/HO-1 in the pathogenesis of arthritis, experimental evidence from cellular and animal models, therapeutic strategies targeting this pathway, and discusses key scientific and technical challenges for future clinical translation.

Across the animal kingdom, neuronal remodeling is a crucial developmental mechanism to refine neurite targeting necessary for both maturation and function of neural circuits. The neuronal chemokine-like Orion is essential for astrocyte infiltration and likely for phagocytosis during mushroom body γ-neuron remodeling during metamorphosis in Drosophila. The Drpr phagocytic receptor is a critical and well-studied regulator of many aspects of neuronal remodeling, where it is required for neurite pruning and cell body removal. In this study, we show a drpr ^null allele displaying a mushroom body (MB)-pruning phenotype very similar, if not identical, to that of orion ^null alleles. Furthermore, when Orion is permanently tethered to the surface of the γ-axons, we show strong genetic interactions between neuronal Orion and glial Drpr. These results strongly suggest that Drpr is the glial receptor for Orion in mushroom body neuronal remodeling.

Introduction: The formation and homeostatic maintenance of cranial sutures rely on cellular activities within the suture mesenchyme. However, how mesenchymal stem/stromal cells (MSCs) rapidly and extensively contribute to suture and cranial development remains insufficiently explored.

Methods: We integrated 10x Genomics and Smart-seq3 single-cell transcriptomic sequencing to analyze cellular subpopulations in the sagittal suture mesenchyme. CytoTRACE2 analysis was performed to quantitatively assess the differentiation status of each cell population. We further characterized the progenitor with characteristics of transient amplifying cells (TACs) via 5-ethynyl-2'-deoxyuridine (EdU) assays, in situ hybridization, and lineage tracing using Ki67Cre^ERT2;tdTomato mice. Through bioinformatics analysis based on sequencing data, we filtered transcription factors of key cell populations.

Results: Smart-seq3 showed higher sequencing depth and improved capture efficiency for target cell populations. Then, we identified a proliferative progenitor population in the sagittal suture that exhibited features of TACs. These TACs were a committed, proliferative direct lineage of suture mesenchymal stem/stromal cells (SuSCs) and responsible for rapid development of cranial structures. Additionally, Erg and E2f7/8 were expressed in SuSCs and TACs, respectively. Among these, Erg downstream targets participated in biological processes governing MSCs and bone morphogenesis processes, while E2f7/8 downstream targets primarily regulate the cell cycle.

Discussion: This study provides the first identification of TACs within the developing cranial suture niche and elucidates key regulatory genes and signaling networks in SuSCs and TACs, thereby providing a theoretical framework for understanding the mechanisms underlying cranial suture formation and homeostasis.