Chitosan oligosaccharides packaged into rat adipose mesenchymal stem cells-derived extracellular vesicles facilitating cartilage injury repair and alleviating osteoarthritis

Shenglong Li,Jie Liu,Weijie Jiao,Xiaohong Wang,Siyu Liu

doi:10.1186/s12951-021-01086-x

Abstract

ObjectivesThis study aimed to investigate the roles of adipose mesenchymal stem cell (AMSC)-derived extracellular vesicles (EVs) binding with chitosan oligosaccharides (COS) in cartilage injury, as well as the related mechanisms.ResultsIL-1β treatment significantly inhibited the viability and migration of chondrocytes and enhanced cell apoptosis (P < 0.05), while chitosan oligosaccharides and extracellular vesicles-chitosan oligosaccharide conjugates (EVs-COS/EVs-COS conjugates) reversed the changes induced by IL-1β (P < 0.05), and the effects of extracellular vesicles-chitosan oligosaccharide conjugates were better than those of chitosan oligosaccharides (P < 0.05). After cartilage damage, IL-1β, OPN, and p53 were significantly upregulated, COL1A1, COL2A1, OCN, RUNX2, p-Akt/Akt, PI3K, c-Myc, and Bcl2 were markedly downregulated, and extracellular vesicles-chitosan oligosaccharide conjugates reversed the expression induced by cartilage injury. Through sequencing, 760 differentially expressed genes (DEGs) clustered into four expression patterns were associated with negative regulation of the canonical Wnt, PI3K-Akt, AMPK, and MAPK signaling pathways.ConclusionExtracellular vesicles-chitosan oligosaccharide conjugates may serve as a new cell-free biomaterial to facilitate cartilage injury repair and improve osteoarthritis.Graphical

Highlights

Articular cartilage, a non-self-repairing tissue, is mainly composed of water, proteoglycan, and collagen, which together determine the functional characteristics of cartilage tissues [1]
Determination of the optimal concentrations of extracellular vesicles (EVs) and chitosan oligosaccharides (COS) To determine the optimal concentrations of EVs and COS for further experiments, chondrocytes were treated with different concentrations of EVs and COS for 48 h, after which their viability was determined
Identification of rat adipose Mesenchymal stem cells (MSCs) (AMSCs)‐derived EVs, EVs‐COS, and rat chondrocytes EVs isolated from rat AMSCs were characterized using transmission electron microscopy (TEM), NS300 particle size analyzer (NTA), and Western blotting

Summary

Introduction

A non-self-repairing tissue, is mainly composed of water, proteoglycan, and collagen, which together determine the functional characteristics of cartilage tissues [1]. Cartilage injury usually marks the occurrence of tissue degeneration, progressive deterioration, subchondral osteosclerosis, and osteoarthritis (OA) [2]. Drugs used to alleviate the symptoms of OA include steroid injections, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids [5, 6]. The long-term use of these drugs may result in side effects, such as gastrointestinal, renal, and cardiovascular diseases [7]. Nanocomposites, including organic–inorganic, inorganic-inorganic, and bioinorganic nanomaterials, have been reported in bone tissue regeneration engineering, such as hydroxyapatite (HA) with chitosan, polycaprolactone/bioglass, and HA-gelatin nanocomposites [8]. By combining nanotechnology-based drug delivery systems, the bioavailability, pharmacokinetics and pharmacodynamics of drugs in bone tissue can be improved, improving therapeutic efficacy while reducing side effects. More therapeutic strategies are urgently needed to improve cartilage injury repair and manage OA

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