Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine. Exosomes, which are characterized as nanometer-sized extracellular vesicles, are secreted by virtually all types of cells. As the research continues, the complex roles of these intracellular-derived extracellular vesicles in biological processes have gradually unfolded. Exosomes have attracted attention as valuable diagnostic and therapeutic tools for their ability to transfer abundant biological cargos and their intricate involvement in multiple cellular functions. In this review, we provide an overview of the recent applications of exosomes within the field of oral diseases, focusing on inflammation-related bone diseases and oral squamous cell carcinomas. We characterize the exosome alterations and demonstrate their potential applications as biomarkers for early diagnosis, highlighting their roles as indicators in multiple oral diseases. We also summarize the promising applications of exosomes in targeted therapy and proposed future directions for the use of exosomes in clinical treatment.
Humans ; Exosomes ; Quality of Life ; Extracellular Vesicles ; Biomarkers ; Cell Communication ; Mouth Neoplasms

BACKGROUND: Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown. METHODS: Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca 2+ -related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance. RESULTS: Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca 2+ is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments. CONCLUSIONS Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.
Animals ; Humans ; Mice ; Apoptosis ; Bone Marrow Cells ; Cell Communication ; Connexin 43/genetics* ; Gap Junctions/metabolism* ; Imatinib Mesylate/therapeutic use* ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology* ; Mesenchymal Stem Cells/metabolism* ; Tumor Microenvironment ; Calcium/metabolism*

Tunneling nanotube (TNT) is a newly discovered communication mode between animal cells in recent years, which have important physiological and pathological significance. However, the role of TNT in bone biology is still unclear. At present, there are many reports about tunneling nanotubes in bone marrow mesenchymal stem cells, osteoclast precursor cells, osteoblasts and immune cells. This review describes the research advances of TNT and its research progress in bone biology. It looks forward to the research direction of TNT in oral and maxillofacial bone development and bone biology, to provide new strategies for the maintenance of bone homeostasis and the treatment of bone diseases.
Animals ; Bone and Bones ; Nanotubes ; Osteoclasts ; Biology ; Cell Communication/physiology*

Skeletal muscle plays a paramount role in physical activity, metabolism, and energy balance, while its homeostasis is being challenged by multiple unfavorable factors such as injury, aging, or obesity. Exosomes, a subset of extracellular vesicles, are now recognized as essential mediators of intercellular communication, holding great clinical potential in the treatment of skeletal muscle diseases. Herein, we outline the recent research progress in exosomal isolation, characterization, and mechanism of action, and emphatically discuss current advances in exosomes derived from multiple organs and tissues, and engineered exosomes regarding the regulation of physiological and pathological development of skeletal muscle. These remarkable advances expand our understanding of myogenesis and muscle diseases. Meanwhile, the engineered exosome, as an endogenous nanocarrier combined with advanced design methodologies of biomolecules, will help to open up innovative therapeutic perspectives for the treatment of muscle diseases.
Exosomes/physiology* ; Muscle, Skeletal/metabolism* ; Cell Communication ; Homeostasis

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.
Animals ; Mice ; Dark Adaptation ; Light ; Retina ; Retinal Cone Photoreceptor Cells/metabolism* ; Adaptation, Ocular ; Neuroglia/physiology* ; Cell Communication ; Thyroid Hormones

A small proportion of mononuclear diploid cardiomyocytes (MNDCMs), with regeneration potential, could persist in adult mammalian heart. However, the heterogeneity of MNDCMs and changes during development remains to be illuminated. To this end, 12 645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing. Three cardiac developmental paths were identified: two switching to cardiomyocytes (CM) maturation with close CM-fibroblast (FB) communications and one maintaining MNDCM status with least CM-FB communications. Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs (non-pMNDCMs) with minimal cell-cell communications were identified in the third path. The non-pMNDCMs possessed distinct properties: the lowest mitochondrial metabolisms, the highest glycolysis, and high expression of Myl4 and Tnni1. Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4⁺Tnni1⁺ MNDCMs persisted in embryonic and adult hearts. These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data. In conclusion, a novel non-pMNDCM subpopulation with minimal cell-cell communications was unveiled, highlighting the importance of microenvironment contribution to CM fate during maturation. These findings could improve the understanding of MNDCM heterogeneity and cardiac development, thus providing new clues for approaches to effective cardiac regeneration.
Animals ; Mice ; Diploidy ; Heart ; Myocytes, Cardiac/metabolism* ; Cell Communication ; Gene Expression Profiling ; Mitochondria ; Regeneration ; Mammals/genetics*

Chronological aging is the leading risk factor for human diseases, while aging at the cellular level, namely cellular senescence, is the fundamental driving force of organismal aging. The impact of cellular senescence on various life processes, including normal physiology, organismal aging and the progress of various age-related pathologies, has been largely ignored for a long time. However, with recent advancement in relevant fields, cellular senescence has become the core of aging biology and geriatric medicine. Although senescent cells play important roles in physiological processes including tissue repair, wound healing, and embryonic development, they can also contribute to tissue dysfunction, organ degeneration and various pathological conditions during adulthood. Senescent cells exert paracrine effects on neighboring cells in tissue microenvironments by developing a senescence-associated secretory phenotype, thus maintaining long-term and active intercellular communications that ultimately results in multiple pathophysiological effects. This is regarded as one of the most important discoveries in life science of this century. Notably, selective elimination of senescent cells through inducing their apoptosis or specifically inhibiting the senescence-associated secretory phenotype has shown remarkable potential in preclinical and clinical interventions of aging and age-related diseases. This reinforces the belief that senescent cells are the key drug target to alleviate various aging syndromes. However, senescent cells exhibit heterogeneity in terms of form, function and tissue distribution, and even differ among species, which presents a challenge for the translation of significant research achievements to clinical practice in future. This article reviews and discusses the characteristics of senescent cells, current targeting strategies and future trends, providing useful and valuable references for the rapidly blooming aging biology and geriatric medicine.
Humans ; Adult ; Aged ; Cellular Senescence/genetics* ; Aging ; Apoptosis ; Cell Communication ; Wound Healing/physiology*

Extracellular vesicles (EV),nanoscale vesicles encapsulated by phospholipid bilayers,are rich in biological molecules such as nucleic acids,metabolites,proteins,and lipids derived from parental cells.They are mainly involved in intercellular communication,signal transmission,and material transport and affect the functions of target cells.Ovulation disorders account for a higher proportion in the factors causing infertility which demonstrates increasing incidence year by year.Non-coding RNAs participate in a series of physiological and pathological processes of follicular development,playing a key role in female infertility.This review systematically introduces the types and biological roles of EV and elaborates on the regulation of follicular development from the effects of EV and non-coding RNAs on granulosa cell function,oocyte maturation,ovulation,luteal formation,and steroid hormone synthesis,providing a new idea and a breakthrough point for the diagnosis and treatment of infertility.
Female ; Humans ; Oogenesis/physiology* ; Granulosa Cells ; Extracellular Vesicles/physiology* ; Cell Communication ; RNA, Untranslated ; Infertility

Neurons migrate from their birthplaces to the destinations, and extending axons navigate to their synaptic targets by sensing various extracellular cues in spatiotemporally controlled manners. These evolutionally conserved guidance cues and their receptors regulate multiple aspects of neural development to establish the highly complex nervous system by mediating both short- and long-range cell-cell communications. Neuronal guidance genes (encoding cues, receptors, or downstream signal transducers) are critical not only for development of the nervous system but also for synaptic maintenance, remodeling, and function in the adult brain. One emerging theme is the combinatorial and complementary functions of relatively limited classes of neuronal guidance genes in multiple processes, including neuronal migration, axonal guidance, synaptogenesis, and circuit formation. Importantly, neuronal guidance genes also regulate cell migration and cell-cell communications outside the nervous system. We are just beginning to understand how cells integrate multiple guidance and adhesion signaling inputs to determine overall cellular/subcellular behavior and how aberrant guidance signaling in various cell types contributes to diverse human diseases, ranging from developmental, neuropsychiatric, and neurodegenerative disorders to cancer metastasis. We review classic studies and recent advances in understanding signaling mechanisms of the guidance genes as well as their roles in human diseases. Furthermore, we discuss the remaining challenges and therapeutic potentials of modulating neuronal guidance pathways in neural repair.
Humans ; Axon Guidance/genetics* ; Neurons ; Axons/metabolism* ; Signal Transduction/genetics* ; Cell Communication

Extracellular vesicles (EVs) are lipid bilayer-enclosed structures containing diverse bioactive cargoes that play a major role in intercellular communication in both physiological and pathological conditions. Currently, the field of EV-based therapy has been rapidly growing, and two main therapeutic uses of EVs can be surmised: (i) exploiting stem cell-derived EVs as therapeutic agents; and (ii) employing EVs as natural therapeutic vectors for drug delivery. This review will discuss the recent advances in EV-based therapy in the treatment of renal disease.
Cell Communication ; Drug Delivery Systems ; Extracellular Vesicles ; Humans ; Kidney Diseases/therapy*