Deer Antler ASCs Exosomes Ameliorate Osteoarthritis via miR-140/MMP13 Axis-Mediated Dual Modulation of Inflammation and Cartilage Regeneration
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PROVIDER: PRJNA1314021 | ENA |
REPOSITORIES: ENA
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Project description:Osteoarthritis (OA) is a progressive degenerative joint disorder characterized by chondrocyte dysfunction and extracellular matrix degradation. While stem cell therapies have been constrained by immunological rejection risks, their derived extracellular vesicles (Exos) emerge as a promising alternative therapeutic approach. Antler, a remarkable regenerative organ with extraordinary regenerative capacity and chondrogenic potential, offers a unique biological resource. Antler Stem Cells (ASCs) provide an innovative extracellular vesicle source (ASC-Exos) that presents a compelling therapeutic strategy for addressing OA's complex pathogenesis. To investigate the therapeutic effects and mechanism of ASC-Exos in OA treatment. ASCs characteristics were confirmed through immunofluorescence and tri-lineage differentiation, while exosomes were validated using transmission electron microscopy, nanoparticle tracking analysis, and Western blot. A rat OA model was established to evaluate therapeutic effects of ASC-Exos via different administration routes. Small RNA sequencing identified key extracellular vesicle components, while dual-luciferase reporter assays confirmed regulatory interactions between miR-140 and metalloproteinase-13(MMP13). Stable miR-140 overexpressing ASCs were generated through lentiviral transduction. An IL-1β-stimulated chondrocyte OA model was employed to assess the impact of miR-140-engineered ASC-Exos (miR-140-Exos) on cellular proliferation, migration, and apoptosis. The therapeutic potential was further evaluated in in vivo animal models. We successfully isolated and characterized ASCs and ASC-Exos. Intra-articular injection of ASC-Exos demonstrated superior cartilage repair efficacy. The critical extracellular vesicle component miR-140 was identified. In vitro studies revealed that miR-140-Exos significantly enhanced chondrocyte proliferation and migration while reducing cellular apoptosis. Dual-luciferase assays confirmed miR-140 directly targets MMP13, with MMP13 overexpression partially reversing miR-140-mediated cellular effects. In vivo investigations demonstrated that miR-140-modified ASC-Exos effectively inhibited COL II degradation and suppressed NLRP3 elevation, thereby providing anti-inflammatory benefits and promoting cartilage regeneration. miR-140-Exos represent an innovative therapeutic approach for osteoarthritis, effectively promoting cartilage regeneration and alleviating inflammation through MMP13 inhibition, presenting a novel therapeutic strategy for OA treatment.
2025-09-03 | GSE306940 | GEO
Project description:To obtain an overview of the antler tip gene expression profile during rapid growth period, a cDNA sample was prepared from antler tip and sequenced using the Illumina sequencing platform.
2011-10-25 | E-MTAB-802 | biostudies-arrayexpress
Project description:we used proteomic technology to disclose the difference of antler regeneration between red deer and sika deer. Through functional analysis, we obtained differentially expressed proteins and the pathway involved in antler regeneration between two groups
2019-06-18 | PXD012090 | Pride
Project description:Identification of the changes in gene expression between the antler velvet and mesenchyme, pedicle skin and frontal skin tissues from adult male deers (Cervus elaphus). Hybridization data were analysed using MAS5, RMA, GCRMA and Dchip algorithms to maximize the chances of identifying gene expression changes. Comparison of 4 tissues with 3 biological replicates each. Samples were obtained from Velvet, Mesenchyme, Pedicle, and Frontal tissues of 3 adult males.
2010-12-31 | E-GEOD-20036 | biostudies-arrayexpress
Project description:Identification of the changes in gene expression between the antler velvet and mesenchyme, pedicle skin and frontal skin tissues from adult male deers (Cervus elaphus). Hybridization data were analysed using MAS5, RMA, GCRMA and Dchip algorithms to maximize the chances of identifying gene expression changes.
2010-12-31 | GSE20036 | GEO
Project description:The therapeutic functions of stem cells were mainly depending on paracrine effects rather than their own proliferation and differentiation on site. In advantage of easy to collected from conditioned medium, have contents of cytokines, growth factors, signaling lipids, mRNAs, and regulatory miRNAs, exosomes from stem cells were considered to be a promising material for stem cell-based cell-free therapies. In traditional Chinese medicine, antler extracts have been used to alleviates aging and aging related diseases. We have demonstrated that exosomes from antler stem cells (ASCs), the source of the annual full regeneration of deer antler, could alleviate cellular senescence and aging related diseases. With exosomes treatment, the senescent phenotype of primary MSCs and hMSCs at late passage were significantly mitigated. When injected into articular cavity, exosomes from ASCs markedly promote joint function recovery and bone and cartilage regeneration. By LC-MS/MS assay, we found that exosomes from ASCs contain various proteins which in the regulation of biological processes including cell proliferation and migration, immunoregulation, wound healing and angiogenesis. With the advantages of abundant sources, low risk of tumorigenicity and immunogenicity, exosomes from ASCs may consider as a promising bio-material for cell-free therapies in the future.
2021-04-21 | GSE172430 | GEO
Project description:Deer antlers are amazing natural appendages that grow faster than any other known mammalian bone. Antler growth occurs at the tip and is initially cartilage, which is later replaced by bone tissue. However, little is known regarding the precise role of cooperation between cell lineages and functional genes in regulating antler growth, and molecular mechanisms responsible for rapid growth remain elusive. In this study, we use an RNA-Seq approach to identify miRNA expression patterns during antler growth.
2017-10-30 | GSE106167 | GEO
Project description:Purpose: The goal of this study is to compare (RNA-seq) transcriptomes of in vitro cultured human bone marrow-derived mesenchymal stem cells (hMSCs) and fallow deer antler-derived skeletal progenitors (FD RM Cells) under multiple conditions to identify candidate proliferation and mineralization genes responsible for fast antler regeneration Methods: hMSCs and FD RM Cells were cultured in vitro under 1) serum-free (0% serum) or serum (10% serum) conditions for 2.5 days or 2) Control (0 ng/mL BMP-2 and 0 nM dexamethasone) and osteogenic (100 ng/mL BMP-2 and 100 nM dexamethasone) media for 24 days. mRNA profiles were generated by deep sequencing, in duplicate, using Illumina HiSeq 2000. The sequence reads were analyzed at the transcript isoform level STARS followed by Cufflinks. Validation for genes of interest was performed using immunofluorescence staining. Results: Comparison of human and fallow deer skeletal progenitor datasets yielded proliferation and mineralization gene candidates Conclusions: Our study represents the first detailed analysis of human and fallow deer transcriptomes of skeletal progenitor cells under proliferation and mineralization conditions, with biologic replicates, generated by RNA-seq technology. Our in vitro comparative approach circumvent some of the logistical and technical challenges in identifying candidate proliferation and mineralization genes responsible for rapid deer antler regeneration. We conclude that in vitro comparison of RNA-seq based transcriptomes identified candidate proliferaiton and mineralization genes to advance bone biology and holds promise to rapidly regenerate large bone volumes for regenerative medicine. The comparative approach utilized here can be adapted for almost any tissue to study a specific phenomenon of interest.
2018-11-16 | GSE89796 | GEO
Project description:To obtain an overview of the antler tip gene expression profile during the ossification stage, a cDNA sample was prepared from antler tip and sequenced using the Illumina sequencing platform.
2012-11-02 | E-MTAB-853 | biostudies-arrayexpress
Project description:As the only regenerative organ of mammals, antler could grow rapidly without carcinogenesis. To understand the molecular mechanisms of the growth of sika deer antler, we used de novo RNA-seq analyses to determine the differential expression of unigenes and miRNAs from antler at 15, 60, 90, and 110-day. A total of 55004 unigenes, 208 known miRNAs and 38 novel miRNAs were identified. 10182 unigenes and 35 miRNAs were differentially expressed between 60-day and 15-day antler, 13258 unigenes and 53 miRNAs were differentially expressed between 90-day and 60-day antler, and 10740 unigenes and 27 miRNAs were differentially expressed between 110-day and 90-day antler. GO and KEGG analyses showed that DE unigenes and miRNA were mainly related to chondrogenesis, osteogenesis and inhibition of oncogenesis, that were closely associate with antler growth. We also constructed mRNA-mRNA and miRNA-mRNA interaction networks related to chondrogenesis, osteogenesis and inhibition of oncogenesis of antler. The results showed that mRNA (COL2A1, SOX9, WWP2, FGFR1, SPARC, LOX etc.) and miRNAs (miR-145, miR-199a-3p, miR-140, miR-199a-5p etc.) may play important roles in chondrogenesis and osteogenesis of antler, and mRNA (TP53, Tpm3 and ATP1A1 etc.) and miRNAs (miR-106a, miR-145, miR-1260b and miR-2898 etc.) may have key roles in inhibiting the carcinogenesis of antlers. In this study, we identified miRNAs and unigenes related to chondrogenesis, osteogenesis and inhibition of oncogenesis of antler. This will provide a reference for in-depth analysis of the molecular mechanism of antler growth without carcinogenesis, and also provide valuable information for cartilage- and bone-related disease treatment, cancer treatment.
2020-12-17 | GSE163384 | GEO