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Keywords = BMP-signalling

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16 pages, 3434 KB  
Article
Transcriptomic Analysis of the Effects of Hydroxysafflor Yellow A on hUC-MSC Senescence via the ECM–Receptor Interaction Pathway
by Siyun Wang, Qi Zhu, Xueer Feng, Xinghua Chou and Tao Lu
Int. J. Mol. Sci. 2025, 26(19), 9579; https://doi.org/10.3390/ijms26199579 - 1 Oct 2025
Abstract
This study investigated the mechanism of hydroxysafflor yellow A (HSYA) on senescent human umbilical cord mesenchymal stem cells (hUC-MSCs) through transcriptome sequencing. HSYA treatment identified 2377 differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed [...] Read more.
This study investigated the mechanism of hydroxysafflor yellow A (HSYA) on senescent human umbilical cord mesenchymal stem cells (hUC-MSCs) through transcriptome sequencing. HSYA treatment identified 2377 differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that these DEGs were primarily enriched in cell adhesion regulation and the extracellular matrix (ECM)–receptor interaction pathway. Gene Set Enrichment Analysis (GSEA) and protein–protein interaction (PPI) network analysis corroborated the central role of ECM–receptor interaction signaling, and Key Driver Analysis (KDA) revealed 10 core regulatory genes (e.g., ID1, SMAD3, TGFB3). SA-β-gal staining showed that HSYA significantly reduced senescence-associated β-galactosidase activity. Flow cytometry showed no significant changes in cell cycle distribution. Western blot analysis indicated that HSYA treatment reduced the protein expression level of p16 without significantly altering p53 levels. Furthermore, HSYA significantly attenuated intracellular reactive oxygen species (ROS) accumulation. qPCR validation demonstrated that HSYA significantly upregulated ID1, GDF5, SMAD3, and TGFB3 while downregulating BMP4, TGFB2, and CCN2. These findings indicate that HSYA modulates genes associated with the ECM–receptor interaction pathway, potentially contributing to improved ECM homeostasis in senescent hUC-MSCs. Full article
(This article belongs to the Section Molecular Informatics)
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41 pages, 1997 KB  
Review
COMP Is a Biomarker of Cartilage Destruction, Extracellular Matrix and Vascular Remodeling and Tissue Repair
by Margaret M. Smith and James Melrose
Int. J. Mol. Sci. 2025, 26(18), 9182; https://doi.org/10.3390/ijms26189182 - 19 Sep 2025
Viewed by 444
Abstract
This review covers the roles of cartilage oligomeric matrix protein (COMP), an established biomarker of cartilage breakdown in pathological tissues in osteoarthritis, and in emerging areas in extracellular matrix and vascular remodeling associated with trauma, fibrosis and cancer. COMP is produced by chondrocytes, [...] Read more.
This review covers the roles of cartilage oligomeric matrix protein (COMP), an established biomarker of cartilage breakdown in pathological tissues in osteoarthritis, and in emerging areas in extracellular matrix and vascular remodeling associated with trauma, fibrosis and cancer. COMP is produced by chondrocytes, tenocytes, myofibroblasts, and in some specialized tissue contexts, endothelial and vascular smooth muscle cells. COMP expression by tendon and cartilage cells is sensitive to weight bearing and tensional mechanical stimulation. Vascular smooth muscle cells are sensitive to shear forces which regulate COMP expression in vascular tissues in atherosclerosis and in carotid stenosis. COMP is a multivalent bridging molecule that stabilizes tissues. It facilitates the signaling of TGF-β and BMP-2 in chondrogenesis, osteogenesis, tissue fibrosis, vascular and ECM remodeling and tumor development by providing a multimeric environment through which growth factor binding and receptor activation can occur. Engineered COMP proteins have been used as molecular templates in the development of chimeric therapeutic proteins of potential application in repair biology. Tie2 (Angiopoietin-1 receptor, Tyrosine-protein kinase receptor TEK), when activated by an engineered COMP-inspired angiopoietin-2 pentamer, is a potent angiogenic molecule of obvious application in wound healing. COMP’s multifunctional properties show it is much more than a biomolecular marker protein through its ability to participate in many biological processes. Further studies are warranted to fully explore the biology of this fascinating molecule, particularly in the wound repair processes. Full article
(This article belongs to the Special Issue Molecular Research on Osteogenesis)
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12 pages, 1047 KB  
Article
Interaction Between Thyroid Hormones and Bone Morphogenetic Proteins in the Regulation of Steroidogenesis by Granulosa Cells
by Kanon Motohashi, Yoshiaki Soejima, Koichiro Yamamoto, Nahoko Iwata, Atsuhito Suyama, Yasuhiro Nakano and Fumio Otsuka
Int. J. Mol. Sci. 2025, 26(18), 9127; https://doi.org/10.3390/ijms26189127 - 18 Sep 2025
Viewed by 289
Abstract
Thyroid hormones are fundamental regulators of cellular differentiation, development, and metabolism. Their receptors are expressed in reproductive tissues, including the ovary, and dysregulation of thyroid hormone homeostasis has been associated with menstrual disturbances, infertility, and adverse pregnancy outcomes. Bone morphogenetic protein (BMP) ligands [...] Read more.
Thyroid hormones are fundamental regulators of cellular differentiation, development, and metabolism. Their receptors are expressed in reproductive tissues, including the ovary, and dysregulation of thyroid hormone homeostasis has been associated with menstrual disturbances, infertility, and adverse pregnancy outcomes. Bone morphogenetic protein (BMP) ligands and their receptors are functionally involved in gonadotropin-induced ovarian steroidogenesis in an autocrine or paracrine manner. In this study, we examined the effects of thyroid hormones on steroidogenesis and their interplay with BMP signaling by using human granulosa-like KGN cells and primary rat granulosa cells (GCs). In KGN cells, triiodothyronine (T3) enhanced forskolin-induced expression of key steroidogenic enzymes involved in both estradiol biosynthesis and progesterone synthesis/metabolism, whereas thyroxine (T4) exerted minimal effects. In rat GCs, T3 treatment increased follicle-stimulating hormone (FSH)-stimulated estradiol production without altering progesterone output. T3 pretreatment attenuated BMP-6-induced phosphorylation of Smad1/5/9 in KGN cells, accompanied by upregulation of inhibitory Smad6 and downregulation of the BMP type II receptor. Conversely, BMP-6 stimulation elevated thyroid hormone receptor β expression, indicating reciprocal regulatory interactions between thyroid hormone and BMP pathways. Collectively, these findings suggest that thyroid hormones modulate steroidogenesis, at least in part, through suppression of endogenous BMP-6 signaling in granulosa cells. Full article
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21 pages, 6074 KB  
Article
Therapeutic Potential of Probiotic-Derived P8 Protein as an Anti-Metastatic Agent in Colorectal Cancer
by Byung Chull An, Seungwoo Kim, Jaewon Ha, Sang-Hyuk Seok, Jun Won Park, Yongku Ryu and Myung Jun Chung
Microorganisms 2025, 13(9), 2175; https://doi.org/10.3390/microorganisms13092175 - 17 Sep 2025
Viewed by 297
Abstract
We previously described the use of probiotics to deliver a Lactobacillus rhamnosus-derived therapeutic protein, P8, which has been identified as a candidate colorectal cancer (CRC) suppressor protein with anti-proliferation and anti-migration activities. P8 was found to penetrate cell membranes by endocytosis, suppressing [...] Read more.
We previously described the use of probiotics to deliver a Lactobacillus rhamnosus-derived therapeutic protein, P8, which has been identified as a candidate colorectal cancer (CRC) suppressor protein with anti-proliferation and anti-migration activities. P8 was found to penetrate cell membranes by endocytosis, suppressing cell proliferation through G2 cell cycle arrest. Despite the ability of P8 to suppress cell migration in vitro, its mechanism of action in CRC is unclear. We profiled the P8-interacting partner proteins using the pull-down method with His-tagged bait P8 and then identified them by LC-MS/MS. Among the interacting targets, we focused on the mothers against decapentaplegic homolog 1 (Smad1), which is well known as one of the important modulators of the bone morphogenetic protein (BMP)-derived migration pathway in CRC. The present study discovers that P8 prevents the phosphorylation of Smad1 or heterologous complexes within the Smad family, interfering with the importation of Smad1 or its complexes into the nucleus. Thus, P8 significantly inhibits the up-regulation of epithelial–mesenchymal transition (EMT)-related genes mediated by Smad1. P8 also inhibits the morphological changes required for cell migration or adhesion. P8 induces morphologic changes in DLD-1 cells, and their spheroid surfaces, resulting in a significant reduction of the number and length of filopodia, as well as the down-regulation of the expression of myosin X and its accumulation in filopodia tips. This phenomenon seems to be a major negative regulator of cell motility that could be of key importance in metastasis. Use of a mouse model of human CRC metastasis confirmed that P8 significantly suppresses the liver metastatic rate. Probiotic-derived protein P8 significantly suppresses CRC metastasis through inhibition of the Smad1-EMT signal pathway and cell–cell adhesion. Full article
(This article belongs to the Topic News and Updates on Probiotics)
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32 pages, 2307 KB  
Review
The Colonic Crypt: Cellular Dynamics and Signaling Pathways in Homeostasis and Cancer
by Anh L. Nguyen, Molly A. Lausten and Bruce M. Boman
Cells 2025, 14(18), 1428; https://doi.org/10.3390/cells14181428 - 11 Sep 2025
Viewed by 634
Abstract
The goal of this review is to expand our understanding of how the cellular organization of the normal colonic crypt is maintained and elucidate how this intricate architecture is disrupted during tumorigenesis. Additionally, it will focus on implications for new therapeutic strategies targeting [...] Read more.
The goal of this review is to expand our understanding of how the cellular organization of the normal colonic crypt is maintained and elucidate how this intricate architecture is disrupted during tumorigenesis. Additionally, it will focus on implications for new therapeutic strategies targeting Epithelial–Mesenchymal Transition (EMT). The colonic crypt is a highly structured epithelial unit that functions in maintaining homeostasis through a complex physiological function of diverse cell types: SCs, transit-amplifying (TA) progenitors, goblet cells, absorptive colonocytes, Paneth-like cells, M cells, tuft cells, and enteroendocrine cells. These cellular subpopulations are spatially organized and regulated by multiple crucial signaling pathways, including WNT, Notch, Bone Morphogenetic Protein (BMP), and Fibroblast Growth Factor (FGF). Specifically, we discuss how these regulatory networks control the precise locations and functions of crypt cell types that are necessary to achieve cellular organization and homeostasis in the normal colon crypt. In addition, we detail how the crypt’s hierarchical structure is profoundly perturbed in colorectal cancer (CRC) development. Tumorigenesis appears to be driven by LGR5+ cancer stem cells (CSCs) and the hyperproliferation of TA cells as colonocytes undergo metabolic reprogramming. Goblet cells lose their secretory phenotype, while REG4+ Paneth-like cells foster SC niches. Tumor microenvironment is also disrupted by upregulation of M cells and by tumor-immune crosstalk that is promoted by tuft cell expansion. Moreover, the presence of enteroendocrine cells in CRC has been implicated in treatment resistance due to its contribution to tumor heterogeneity. These cellular changes are caused by the disruption of homeostasis signaling whereby: overactivation of WNT/β-catenin promotes stemness, dysregulation of Notch inhibits differentiation, suppression of BMP promotes hyperproliferation, and imbalance of FGF/WNT/BMP/NOTCH enhances cellular plasticity and invasion. Further discussion of emerging therapies targeting epithelial markers and regulatory factors, emphasizing current development in novel, precision-based approaches in CRC treatment is also included. Full article
(This article belongs to the Section Tissues and Organs)
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15 pages, 1767 KB  
Review
Signaling Pathways in Human Blastocyst Development: From Molecular Mechanisms to In Vitro Optimization
by Yan Jiao, Jiapeng Liu, Congge Li, Yuexin Hu and Sanjun Zhao
J. Dev. Biol. 2025, 13(3), 33; https://doi.org/10.3390/jdb13030033 - 9 Sep 2025
Viewed by 536
Abstract
In recent years, assisted reproductive technology (ART) has developed rapidly with the delay in reproductive age and the rise in infertility rates. During ART, blastocyst quality is a key factor affecting the rate of implantation and clinical pregnancy, and blastocyst formation is dependent [...] Read more.
In recent years, assisted reproductive technology (ART) has developed rapidly with the delay in reproductive age and the rise in infertility rates. During ART, blastocyst quality is a key factor affecting the rate of implantation and clinical pregnancy, and blastocyst formation is dependent on the precise regulation of multiple signaling pathways in preimplantation embryo development. In this review, we systematically analyze the molecular mechanisms of the core pathways, including Hippo, Wnt/β-catenin, FGF, Nodal, and BMP, in blastocyst lineage differentiation and morphogenesis, and assess the feasibility of optimizing in vitro culture by targeting key signaling nodes, as well as provide theoretical support for constructing research models of preimplantation embryos. Full article
(This article belongs to the Collection Hedgehog Signaling in Embryogenesis)
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13 pages, 628 KB  
Review
Research Progress on the Molecular Mechanism of Poultry Feather Follicle Development
by Jiangxian Wang, Shiliang Zhu, Xia Xiong, Mohan Qiu, Zengrong Zhang, Chenming Hu, Li Yang, Han Peng, Xiaoyan Song, Jialei Chen, Bo Xia, Zhuxiang Xiong, Longhuan Du, Chunlin Yu and Chaowu Yang
Curr. Issues Mol. Biol. 2025, 47(9), 684; https://doi.org/10.3390/cimb47090684 - 25 Aug 2025
Viewed by 599
Abstract
The evolution of the chilled processing technology has precipitated the emergence of ice-fresh poultry meat as a significant sales channel. The aesthetic appearance of chicken carcasses has become increasingly important in the context of poultry ice-fresh sales, in conjunction with the comprehensive implementation [...] Read more.
The evolution of the chilled processing technology has precipitated the emergence of ice-fresh poultry meat as a significant sales channel. The aesthetic appearance of chicken carcasses has become increasingly important in the context of poultry ice-fresh sales, in conjunction with the comprehensive implementation of China’s policies for poultry. Feather follicle development is a significant factor in determining the aesthetic appearance of the carcass. Recent studies have focused on the molecular mechanisms associated with feather follicle development. The WNT, EGF, FGF, SHH, and BMP signalling pathways have been identified as the regulatory mechanisms involved in the development of feather follicles in various segments of poultry skin. However, the BMP signalling pathway, acting as an inhibitor, has been demonstrated to impede the regulatory processes governing feather follicle development via these signalling pathways. This review summarises the structure and overview of feathers and feather follicles, the research progress of signalling pathways that affect the development of poultry feather follicles, the research progress of poultry follicle traits, and the research progress of feather follicle development biotechnology. The present review focuses on summarising the molecular mechanisms that affect feather follicle development, and on providing a summary of the application of biotechnology in this field. It also offers ideas and theoretical references for the molecular mechanism of poultry feather follicle development. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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17 pages, 2760 KB  
Article
Hemp Seed-Derived Exosomes Protect Against Dihydrotestosterone-Induced Chicken Feather Growth Inhibition
by Hwapyung Kim, Gwangpyung Kim, Namsoo Peter Kim and Boyong Kim
Pharmaceuticals 2025, 18(8), 1192; https://doi.org/10.3390/ph18081192 - 13 Aug 2025
Viewed by 508
Abstract
Background/Objectives: Androgenetic alopecia suppresses hair follicle growth. This occurs via dihydrotestosterone (DHT), which inhibits key molecular pathways such as Wnt/β-catenin and Sonic Hedgehog (SHH) signaling. Exosomes derived from plant callus cultures are promising biomaterials for targeted delivery and regenerative medicine. This study aimed [...] Read more.
Background/Objectives: Androgenetic alopecia suppresses hair follicle growth. This occurs via dihydrotestosterone (DHT), which inhibits key molecular pathways such as Wnt/β-catenin and Sonic Hedgehog (SHH) signaling. Exosomes derived from plant callus cultures are promising biomaterials for targeted delivery and regenerative medicine. This study aimed to investigate the protective effects of hemp seed callus-derived exosomes (E40) against DHT-induced inhibition of feather follicle development in a chicken embryo model. Methods: E40 exosomes were isolated and purified from the calli of germinated hemp seeds. A DHT-induced feather loss model was established by injecting chicken embryos on embryonic day 7 (E7) with DHT (50 ng/mL), with or without co-administration of E40 (40 µg/mL). On embryonic day 12 (E12), feather length, density, and expression of molecular markers were analyzed. The methods included FISH, Western blotting, and quantitative analysis of PTCH1, AR, SHH, SMO, GLI1, Wnt, β-catenin, BMP4, and Noggin. Results: DHT treatment significantly reduced feather length and density. It also downregulated SHH and Wnt/β-catenin markers, upregulating BMP4 and androgen receptor expression. Co-treatment with E40 restored feather length and density to levels comparable to controls and significantly recovered the expression of SHH, SMO, GLI1, Wnt, and β-catenin. E40 also suppressed DHT-induced BMP4 upregulation by approximately 30% and reduced androgen receptor expression. Conclusions: These results suggest that hemp seed-derived exosomes (E40) effectively mitigate DHT-induced feather follicle inhibition by modulating critical signaling pathways and immune-related markers, supporting their potential application as a nanocarrier-based therapeutic strategy for alopecia management. Full article
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23 pages, 1226 KB  
Article
Multi-Layered Analysis of TGF-β Signaling and Regulation via DNA Methylation and microRNAs in Astrocytic Tumors
by Klaudia Skóra, Damian Strojny, Dawid Sobański, Rafał Staszkiewicz, Paweł Gogol, Mateusz Miller, Przemysław Rogoziński, Nikola Zmarzły and Beniamin Oskar Grabarek
Int. J. Mol. Sci. 2025, 26(16), 7798; https://doi.org/10.3390/ijms26167798 - 12 Aug 2025
Viewed by 458
Abstract
Astrocytic tumors are a heterogeneous group of glial neoplasms characterized by marked differences in biological behavior and patient prognosis. Transforming growth factor-beta (TGF-β) signaling plays a pivotal role in astrocytoma pathogenesis; however, the extent and mechanisms of its epigenetic regulation remain poorly understood. [...] Read more.
Astrocytic tumors are a heterogeneous group of glial neoplasms characterized by marked differences in biological behavior and patient prognosis. Transforming growth factor-beta (TGF-β) signaling plays a pivotal role in astrocytoma pathogenesis; however, the extent and mechanisms of its epigenetic regulation remain poorly understood. This study aimed to investigate how promoter methylation and microRNA-mediated mechanisms regulate key genes within the TGF-β signaling pathway across various astrocytoma grades. Tumor tissue samples from 65 patients with WHO grade II–IV astrocytomas were analyzed using Affymetrix gene expression and microRNA microarrays. Promoter methylation of TGF-β signaling genes was assessed using methylation-specific polymerase chain reaction (MSP). Gene expression was validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), and protein levels were quantified using enzyme-linked immunosorbent assay (ELISA). MicroRNA targets were predicted using bioinformatic tools, and survival analyses were conducted using Kaplan–Meier and Cox regression models. Six genes—SMAD1, SMAD3, SKIL, BMP2, SMAD4, and MAPK1—showed significant upregulation in high-grade tumors (fold change > 5.0, p < 0.05), supported by RT-qPCR and protein-level data. Promoter hypomethylation and reduced expression of regulatory microRNAs (e.g., hsa-miR-145-5p targeting SMAD3) were more common in higher-grade tumors. Protein–protein interaction analysis indicated strong functional interconnectivity among the overexpressed genes. High protein levels of SMAD1, SMAD3, and SKIL were significantly associated with shorter overall survival (p < 0.001). This multi-level analysis reveals that astrocytic tumor progression involves epigenetic derepression and microRNA-mediated dysregulation of TGF-β signaling. Elevated expression of SMAD1, SMAD3, and SKIL emerged as strong prognostic indicators, underscoring their potential as biomarkers and therapeutic targets in astrocytic tumors. Full article
(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment, 2nd Edition)
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16 pages, 1826 KB  
Article
Epigenetic Signatures of Dental Stem Cells: Insights into DNA Methylation and Noncoding RNAs
by Rosanna Guarnieri, Agnese Giovannetti, Giulia Marigliani, Michele Pieroni, Tommaso Mazza, Ersilia Barbato and Viviana Caputo
Appl. Sci. 2025, 15(15), 8749; https://doi.org/10.3390/app15158749 - 7 Aug 2025
Viewed by 578
Abstract
Tooth development (odontogenesis) is regulated by interactions between epithelial and mesenchymal tissues through signaling pathways such as Bone Morphogenetic Protein (BMP), Wingless-related integration site (Wnt), Sonic Hedgehog (SHH), and Fibroblast Growth Factor (FGF). Mesenchymal stem cells (MSCs) derived from dental tissues—including dental pulp [...] Read more.
Tooth development (odontogenesis) is regulated by interactions between epithelial and mesenchymal tissues through signaling pathways such as Bone Morphogenetic Protein (BMP), Wingless-related integration site (Wnt), Sonic Hedgehog (SHH), and Fibroblast Growth Factor (FGF). Mesenchymal stem cells (MSCs) derived from dental tissues—including dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and dental follicle progenitor cells (DFPCs)—show promise for regenerative dentistry due to their multilineage differentiation potential. Epigenetic regulation, particularly DNA methylation, is hypothesized to underpin their distinct regenerative capacities. This study reanalyzed publicly available DNA methylation data generated with Illumina Infinium HumanMethylation450 BeadChip arrays (450K arrays) from DPSCs, PDLSCs, and DFPCs. High-confidence CpG sites were selected based on detection p-values, probe variance, and genomic annotation. Principal Component Analysis (PCA) and hierarchical clustering identified distinct methylation profiles. Functional enrichment analyses highlighted biological processes and pathways associated with specific methylation clusters. Noncoding RNA analysis was integrated to construct regulatory networks linking DNA methylation patterns with key developmental genes. Distinct epigenetic signatures were identified for DPSCs, PDLSCs, and DFPCs, characterized by differential methylation across specific genomic contexts. Functional enrichment revealed pathways involved in odontogenesis, osteogenesis, and neurodevelopment. Network analysis identified central regulatory nodes—including genes, such as PAX6, FOXC2, NR2F2, SALL1, BMP7, and JAG1—highlighting their roles in tooth development. Several noncoding RNAs were also identified, sharing promoter methylation patterns with developmental genes and being implicated in regulatory networks associated with stem cell differentiation and tissue-specific function. Altogether, DNA methylation profiling revealed that distinct epigenetic landscapes underlie the developmental identity and differentiation potential of dental-derived mesenchymal stem cells. This integrative analysis highlights the relevance of noncoding RNAs and regulatory networks, suggesting novel biomarkers and potential therapeutic targets in regenerative dentistry and orthodontics. Full article
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16 pages, 1247 KB  
Review
When Bone Forms Where It Shouldn’t: Heterotopic Ossification in Muscle Injury and Disease
by Anthony Facchin, Sophie Lemaire, Li Gang Toner, Anteneh Argaw and Jérôme Frenette
Int. J. Mol. Sci. 2025, 26(15), 7516; https://doi.org/10.3390/ijms26157516 - 4 Aug 2025
Viewed by 993
Abstract
Heterotopic ossification (HO) refers to the pathological formation of bone in soft tissues, typically following trauma, surgical procedures, or as a result of genetic disorders. Notably, injuries to the central nervous system significantly increase the risk of HO, a condition referred to as [...] Read more.
Heterotopic ossification (HO) refers to the pathological formation of bone in soft tissues, typically following trauma, surgical procedures, or as a result of genetic disorders. Notably, injuries to the central nervous system significantly increase the risk of HO, a condition referred to as neurogenic HO (NHO). This review outlines the cellular and molecular mechanisms driving HO, focusing on the inflammatory response, progenitor cell reprogramming, and current treatment strategies. HO is primarily fuelled by a prolonged and dysregulated inflammatory response, characterized by sustained expression of osteoinductive cytokines secreted by M1 macrophages. These cytokines promote the aberrant differentiation of fibro-adipogenic progenitor cells (FAPs) into osteoblasts, leading to ectopic mineralization. Additional factors such as hypoxia, BMP signalling, and mechanotransduction pathways further contribute to extracellular matrix (ECM) remodelling and osteogenic reprogramming of FAPs. In the context of NHO, neuroendocrine mediators enhance ectopic bone formation by influencing both local inflammation and progenitor cell fate decisions. Current treatment options such as nonsteroidal anti-inflammatory drugs (NSAIDs), radiation therapy, and surgical excision offer limited efficacy and are associated with significant risks. Novel therapeutic strategies targeting inflammation, neuropeptide signalling, and calcium metabolism may offer more effective approaches to preventing or mitigating HO progression. Full article
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25 pages, 1749 KB  
Review
TGF-β Signaling in Cancer: Mechanisms of Progression and Therapeutic Targets
by Elżbieta Cecerska-Heryć, Adrianna Jerzyk, Małgorzata Goszka, Aleksandra Polikowska, Julita Rachwalska, Natalia Serwin, Bartosz Wojciuk and Barbara Dołęgowska
Int. J. Mol. Sci. 2025, 26(15), 7326; https://doi.org/10.3390/ijms26157326 - 29 Jul 2025
Viewed by 1842
Abstract
Transforming growth factor-β (TGF-β) is a key protein family member that includes activins, inhibins, and bone morphogenetic proteins (BMPs). It is essential in numerous biological processes, such as chemotaxis, apoptosis, differentiation, growth, and cell migration. TGF-β receptors initiate signaling through two primary pathways: [...] Read more.
Transforming growth factor-β (TGF-β) is a key protein family member that includes activins, inhibins, and bone morphogenetic proteins (BMPs). It is essential in numerous biological processes, such as chemotaxis, apoptosis, differentiation, growth, and cell migration. TGF-β receptors initiate signaling through two primary pathways: the canonical pathway involving Smad proteins and non-canonical pathways that utilize alternative signaling mechanisms. When TGF-β signaling is disrupted, it has been shown to contribute to the development of various diseases, including cancer. Initially, TGF-β effectively inhibits the cell cycle and promotes apoptosis. However, its role can transition to facilitating tumor growth and metastasis as the disease progresses. Moreover, TGF-β drives cancer progression through epithelial–mesenchymal transition (EMT), modulation of factor expression, and evasion of immune responses. This complexity establishes the need for further research, particularly into pharmacological agents targeting TGF-β, which are emerging as promising therapeutic options. Current clinical and preclinical studies are making significant strides toward mitigating the adverse effects of TGF-β. This underscores the critical importance of understanding its underlying mechanisms to enhance treatment effectiveness and improve survival rates for cancer patients. Full article
(This article belongs to the Special Issue Advancements in Cancer Biomarkers)
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20 pages, 5747 KB  
Article
Functional Study of the BMP Signaling Pathway in Appendage Regeneration of Exopalaemon carinicauda
by Chaofan Xing, Yong Li, Zhenxiang Chen, Qingyuan Hu, Jiayi Sun, Huanyu Chen, Qi Zou, Yingying Li, Fei Yu, Chao Wang, Panpan Wang and Xin Shen
Biology 2025, 14(8), 940; https://doi.org/10.3390/biology14080940 - 25 Jul 2025
Viewed by 661
Abstract
Appendage autotomy frequently occurs during the cultivation of Exopalaemon carinicauda, which severely impacts its survival and economic benefits. To investigate the molecular mechanism underlying appendage regeneration in E. carinicauda, this study presents a comparative transcriptome analysis on samples from different stages [...] Read more.
Appendage autotomy frequently occurs during the cultivation of Exopalaemon carinicauda, which severely impacts its survival and economic benefits. To investigate the molecular mechanism underlying appendage regeneration in E. carinicauda, this study presents a comparative transcriptome analysis on samples from different stages of appendage regeneration in individuals of the same family of E. carinicauda. A total of 6460 differentially expressed genes (DEGs) were identified between the samples collected at 0 h post-autotomy (D0) and those collected at 18 h post-autotomy (D18h). Additionally, 7740 DEGs were identified between D0 and 14 d post-autotomy (D14d), with 3382 DEGs identified between D18h and D14d. Among them, differentially expressed genes such as EcR, RXR, BMP1, and Smad4 are related to muscle growth or molting and may be involved in the regeneration process. qRT-PCR results revealed that EcBMPR2 was expressed at relatively high levels in the gonad and ventral nerve cord tissues and that the highest level of expression was detected in the regenerative basal tissue at 24 h post-autotomy. In situ hybridization results indicated strong signals of this gene in the cells at the wound site at 72 h post-autotomy. Following knockdown of EcBMPR2, the expression levels of both EcBMPR1B and EcSmad1 were significantly downregulated, and long-term interference with the EcBMPR2 gene resulted in a significantly slower appendage regeneration process compared to the control group. When the downstream transcription factor EcSmad1 was knocked down, the two receptor genes EcBMPR2 and EcBMPR1B were downregulated, whereas EcBMP7 was upregulated. After inhibiting the BMP signaling pathway, the degree of cell aggregation at the autotomy site in the experimental group was significantly lower than that in the control group, the wound healing rate was delayed, and the blastema regeneration time was prolonged from 5 d to 7 d. Collectively, these results indicate that the BMP signaling pathway plays a critical role in the early stages of appendage regeneration in E. carinicauda. This study provides important theoretical insights for understanding limb regeneration in crustaceans. Full article
(This article belongs to the Section Physiology)
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18 pages, 3194 KB  
Article
Identification and Characterization of the Complete Genome of the TGF-β Gene Family in Tupaia belangeri: Expression and Function of Adipose Tissue Under Cold Acclimation Conditions
by Lijie Du, Wanlong Zhu and Lin Zhang
Int. J. Mol. Sci. 2025, 26(14), 6681; https://doi.org/10.3390/ijms26146681 - 11 Jul 2025
Viewed by 532
Abstract
The transforming growth factor beta (TGF-β) gene family is widely distributed across the animal kingdom, playing a crucial role in various cellular processes and maintaining overall health and homeostasis. The present study identified 34 TGF-β family genes based on the [...] Read more.
The transforming growth factor beta (TGF-β) gene family is widely distributed across the animal kingdom, playing a crucial role in various cellular processes and maintaining overall health and homeostasis. The present study identified 34 TGF-β family genes based on the genome sequence in Tupaia belangeri, which were classified into the TGF-β, bone morphogenetic protein (BMP), growth differentiation factor (GDF), glial cell-derived neurotrophic factor (GDNF), and Activin/Inhibin subfamilies. A phylogenetic analysis revealed the evolutionary relationships among members of the TGF-β family in T. belangeri and their homologous genes in Homo sapiens, Mus musculus, and Pan troglodytes, indicating a high degree of conservation throughout evolution. A chromosomal distribution and collinearity analysis demonstrated the localization of these genes within the genome of T. belangeri and their collinearity with genes from other species. A gene structure and motif analysis further illustrated the conservation and diversity among TGF-β family members. A protein interaction network analysis highlighted the central roles of TGFB1, TGFB3, BMP7, and BMP2 in signal transduction. A functional enrichment analysis underscored the significance of the TGF-β signaling pathway in the biological processes of T. belangeri, particularly in cell proliferation, differentiation, and apoptosis. We assessed the impact of cold acclimation treatment on the expression of TGF-β family proteins in the adipose tissue (white adipose tissue [WAT] and brown adipose tissue [BAT]) of T. belangeri using ELISA technology, finding that protein expression levels in the experimental group were significantly higher than those of in the control group. These results suggested that cold acclimation may enhance the adaptability of T. belangeri to cold environments by modulating the expression of TGF-β family genes. This study offers new insights into the role of the TGF-β family in the cold acclimation adaptation of T. belangeri, providing a scientific foundation for future genetic improvements and strategies for cold acclimation. Full article
(This article belongs to the Section Molecular Biology)
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16 pages, 8324 KB  
Article
Transcriptomic Differences Between Human Trabecular Meshwork Stem Cells and Trabecular Meshwork Cells Reveal Specific Biomarker Profiles
by Rong Du, Ajay Kumar, Enzhi Yang, Jingxue Zhang, Ningli Wang and Yiqin Du
Curr. Issues Mol. Biol. 2025, 47(7), 514; https://doi.org/10.3390/cimb47070514 - 3 Jul 2025
Cited by 1 | Viewed by 548
Abstract
Glaucoma is a leading cause of irreversible blindness, normally associated with dysfunction and degeneration of the trabecular meshwork (TM) as the primary cause. Trabecular meshwork stem cells (TMSCs) have emerged as promising candidates for TM regeneration toward glaucoma therapies, yet their molecular characteristics [...] Read more.
Glaucoma is a leading cause of irreversible blindness, normally associated with dysfunction and degeneration of the trabecular meshwork (TM) as the primary cause. Trabecular meshwork stem cells (TMSCs) have emerged as promising candidates for TM regeneration toward glaucoma therapies, yet their molecular characteristics remain poorly defined. In this study, we performed a comprehensive transcriptomic comparison of human TMSCs and human TM cells (TMCs) using RNA sequencing and microarray analyses, followed by qPCR validation. A total of 465 differentially expressed genes were identified, with 254 upregulated in TMSCs and 211 in TMCs. A functional enrichment analysis revealed that TMSCs are associated with development, immune signaling, and extracellular matrix remodeling pathways, while TMCs are enriched in structural, contractile, and adhesion-related functions. A network topology analysis identified CXCL3, CXCL6, and BMP2 as robust TMSC-specific hub genes, and LMOD1 and BGN as TMC-specific markers, with expression patterns confirmed by qPCR. These findings define distinct molecular signatures of TMSCs and TMCs, providing reliable biomarkers for cell identity and a foundation for future stem cell-based therapies targeting TM dysfunction in glaucoma. Full article
(This article belongs to the Section Molecular Medicine)
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