miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis.

08:00 EDT 20th March 2019 | BioPortfolio

Summary of "miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis."

Osteoarthritis (OA) is the most common disabling joint disease throughout the world and its therapeutic effect is still not satisfactory in clinic nowadays. Recent studies showed that the exosomes derived from several types of mesenchymal stem cells (MSCs) could maintain chondrocyte homeostasis and ameliorate the pathological severity of OA in animal models, indicating that MSCs-derived exosomes could be a novel promising strategy for treating OA. In this study, we investigated the role and underlying mechanisms of infrapatellar fat pad (IPFP) MSCs-derived exosomes (MSC-Exos) on OA in vitro and in vivo. Our data revealed that MSC could produce amounts of MSC-Exos, which exhibited the typical morphological features of exosomes. The MSC-Exos ameliorated the OA severity in vivo and inhibited cell apoptosis, enhanced matrix synthesis and reduced the expression of catabolic factor in vitro. Moreover, MSC-Exos could significantly enhance autophagy level in chondrocytes partially via mTOR inhibition. Exosomal RNA-seq showed that the level of miR-100-5p that could bind to the 3'-untranslated region (3'UTR) of mTOR was the highest among microRNAs. MSC-Exos decreased the luciferase activity of mTOR 3'UTR, while inhibition of miR-100-5p could reverse the MSC-Exos-decreased mTOR signaling pathway. Intra-articular injection of antagomir-miR-100-5p dramatically attenuated MSC-Exos-mediated protective effect on articular cartilage in vivo. In brief, MSC-derived exosomes protect articular cartilage from damage and ameliorate gait abnormality in OA mice by maintaining cartilage homeostasis, the mechanism of which may be related to miR100-5p-regulated inhibition of mTOR-autophagy pathway. As it is relatively feasible to obtain human IPFP from OA patients by arthroscopic operation in clinic, MSC-derived exosomes may be a potential therapy for OA in the future.


Journal Details

This article was published in the following journal.

Name: Biomaterials
ISSN: 1878-5905
Pages: 87-100


DeepDyve research library

PubMed Articles [8028 Associated PubMed Articles listed on BioPortfolio]

Tenocyte-derived exosomes induce the tenogenic differentiation of mesenchymal stem cells through TGF-β.

Mesenchymal stem cells (MSCs) hold great potential to treat tissue damage based on their multipotent property, and are also considered as suitable cell resources to create tissue-engineered grafts for...

Oral mucosal mesenchymal stem cell‑derived exosomes: A potential therapeutic target in oral premalignant lesions.

Emerging evidence indicates that mesenchymal stem cells (MSCs) serve an indispensable role in the tumor microenvironment. However, whether MSCs participate in the development of oral carcinogenesis r...

Mesenchymal Stromal Cell-Derived Exosomes Attenuate Myocardial Ischemia-Reperfusion Injury through miR-182-Regulated Macrophage Polarization.

Mesenchymal stem cells (MSCs) gradually become attractive candidates for cardiac inflammation modulation, yet understanding of the mechanism remains elusive. Strikingly, recent studies indicated that ...

Human Fetal Liver Mesenchymal Stem Cell derived Exosomes impair NK cell function.

Mesenchymal stem cells (MSCs) are powerful immunomodulators that regulate the diverse functions of immune cells involved in allogeneic reactions, such as T cells and natural killer cells (NK), through...

Bone Marrow Mesenchymal Stem Cells-Derived Exosomal MiR-29b-3p Regulates Aging-Associated Insulin Resistance.

Insulin resistance is the major pathological characteristic of type 2 diabetes and the elderly often develop insulin resistance. However, the deep-seated mechanisms for aging-related insulin resistanc...

Clinical Trials [2480 Associated Clinical Trials listed on BioPortfolio]

MSCs and MSC-Exos Promote Healing of MHs

Purpose: To assess the safety and efficacy of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exos) for promoting healing of large and refractory macular holes (MHs). Hypothes...

Allogenic Mesenchymal Stem Cell Derived Exosome in Patients With Acute Ischemic Stroke

Administration of cell-free exosomes derived from mesenchymal stem cell (MSCs) can be sufficient to exert therapeutic effects of intact MSCs after brain injury. In this study we aim to ass...

Dendritic Cells-Derived Exosomes in Human Sepsis

The amount of peripheral blood exosomes has been confirmed to change in the endotoxin-induced infection. The primary objectives of this study are to compare the changes of peripheral blood...

Effect of Plasma Derived Exosomes on Cutaneous Wound Healing

This study is an open prospective clinical trial. The objective is to evaluate the effect of autologous exosomes rich plasma on cutaneous wound healing. The participants are patients with ...

INfrapatellar Versus SUprapatellar Reamed Intramedullary Nailing for Fractures of the Tibia

This study will investigate the incidence and severity of anterior knee pain comparing two different approaches to tibial nail fixation; Infrapatellar versus percutaneous semi-extended sup...

Medical and Biotech [MESH] Definitions

The joint that is formed by the inferior articular and malleolar articular surfaces of the TIBIA; the malleolar articular surface of the FIBULA; and the medial malleolar, lateral malleolar, and superior surfaces of the TALUS.

Obtaining material for pathological examination and analysis, from bodily fluids. Material retrieved includes CELL-FREE NUCLEIC ACIDS; CELL-DERIVED MICROPARTICLES; EXOSOMES; CIRCULATING NEOPLASM CELLS; and other circulating cells and CELLULAR STRUCTURES.

A water-soluble thiol derived from hydrogen sulfide and ethanol. It is used as a reducing agent for disulfide bonds and to protect sulfhydryl groups from oxidation.

Fractures of the articular surface of a bone.

Large HYALURONAN-containing proteoglycans found in articular cartilage (CARTILAGE, ARTICULAR). They form into aggregates that provide tissues with the capacity to resist high compressive and tensile forces.

Quick Search


DeepDyve research library

Relevant Topic

Arthritis is by definition the inflammation of one or more joints, characterized by swelling, pain, warmth, redness and diminished range of joint movement (Oxford Medical Dictionary). There are many different types; Noninflammatory; Osteoarthritis, N...

Searches Linking to this Article