Abstract This study aimed to elucidate the role of microRNA miR-92a-3p in the pathogenesis of adenomyosis. We focused on understanding how miR-92a-3p in exosomes derived from ectopic lesions influences the behavior of endometrial cells, DRG neurons, and Human Umbilical Vein Endothelial Cells (HUVECs), and its potential as a non-invasive diagnostic biomarker. Our findings revealed that MiR-92a-3p is significantly upregulated in exosomes derived from ectopic lesions of adenomyosis. This upregulation was associated with enhanced migration and invasion capabilities in eutopic endometrial cells, DRG neurons, and HUVECs. Furthermore, the study demonstrated a significant correlation between the levels of MiR-92a-3p in urinary exosomes and the clinical symptoms of adenomyosis, suggesting its potential as a non-invasive biomarker for the disease. This study elucidates an exosomal signaling process via miR-92a-3p that drives pathological infiltration and angiogenesis to promote adenomyosis progression. Upregulated miR-92a-3p in biofluid exosomes shows promising non-invasive biomarker potential for diagnosis and monitoring of this disease. Our findings unveil novel targets and tools for improved clinical management.Our research uncovers the significant role of miR-92a-3p in adenomyosis pathogenesis. We demonstrate that miR-92a-3p, upregulated in exosomes from ectopic lesions, enhances migration and invasion of endometrial cells, DRG neurons, and HUVECs. Crucially, miR-92a-3p levels in urinary exosomes correlate with adenomyosis symptoms, highlighting its potential as a non-invasive biomarker. This study offers new insights into adenomyosis progression and introduces novel diagnostic and therapeutic avenues.
Adenomyosis is a poorly understood gynecological disorder lacking effective treatments. Controversy persists regarding "invagination" and "metaplasia" theories. The endometrial-myometrial junction (EMJ) connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis, but its in-depth study is just beginning. Using single-cell RNA sequencing and spatial profiling, we mapped transcriptional alterations across eutopic endometrium, lesions, and EMJ. Within lesions, we identified unique epithelial (LGR5+) and invasive stromal (PKIB+) subpopulations, along with WFDC1+ progenitor cells, supporting a complex interplay between "invagination" and "metaplasia" theories of pathogenesis. Further, we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving vascular endothelial growth factor and angiopoietin pathways. Cell-cell communication differed markedly between ectopic and eutopic endometrium, with aberrant signaling in lesions involving pleiotrophin, TWEAK, and WNT cascades. This study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified, dysfunctional signaling, and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.
Abstract Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) hold significant potential in the treatment of osteoarthritis (OA). However, simple exosomes therapy often proves insufficiently effective and challenging to achieve optimal therapeutic outcome. Herein, an innovative injectable multifunctional composite hydrogel (Exo shEZH2 @HG) is composed of photocrosslinking partially modified hyaluronic acid with o ‐nitrobenzyl alcohol (HA‐NB), gelatin, and shRNA‐EZH2 endogenously modified exosomes (Exo shEZH2 ), designed for cartilage defects, which are a primary cause of early OA. It exhibits rapid and controllable photo‐induced gelation characteristics, resembling human cancellous bone compressive strength, and boasting excellent biocompatibility. In vitro studies indicate that Exo shEZH2 @HG slowly releases Exo shEZH2 , promoting the migration and infiltration of BMSCs into surrounding tissues. By inhibiting the overexpression of EZH2, Exo shEZH2 suppresses histone hypermethylation and the nuclear factor kappa‐B (NF‐κB) signaling pathway, thereby inhibiting inflammation and apoptosis in chondrocytes. Simultaneously, it promotes the regeneration of the extracellular matrix and the chondrogenic differentiation of BMSCs. Within a rat cartilage defect model, Exo shEZH2 @HG significantly facilitates the regeneration of cartilage tissue resembling hyaline cartilage in the defect area, preventing the progression of OA. In summary, this multifunctional composite hydrogel offers a promising approach for the treatment of cartilage defects and the prevention of OA through multiple synergistic effects.
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