Exosomes from adipose‑derived stem cells promote chondrogenesis and suppress inflammation by upregulating miR‑145 and miR‑221

Abstract

osteoarthritis (oa) is one of the most prevalent joint disorders globally. Patients suffering from oa are often obese and adiposity is linked to chronic inflammation. In the present study, the potential of using exosomes isolated from adipose-derived stem cells (adScs) as a therapeutic tool for reducing chronic inflammation and promoting chondrogenesis was investigated using patient-derived primary cells. First, it was tested whether patient-derived adScs could differentiate into chondrogenic and osteogenic lineages. The adScs were then used as a source of exosomes. it was found that exosomes isolated from adScs, when co-cultured with activated synovial fibroblasts, downregulated the expression of pro-inflammatory markers interleukin (il)-6, nF-κB and tumor necrosis factor-α, while they upregulated the expression of the anti-inflammatory cytokine IL-10; without exosomes, the opposite observations were made. in addition, inflammation-inflicted oxidative stress was induced in vitro by stimulating chondrocytes with H 2 o 2 . Treatment with exosomes protected articular chondrocytes from H 2 o 2 -induced apoptosis. Furthermore, exosome treatment promoted chondrogenesis in periosteal cells and increased chondrogenic markers, including collagen type ii and β-catenin; inhibition of Wnt/β-catenin, using the antagonist icG-001, prevented exosome-induced chondrogenesis. Periosteal cells treated with exosomes exhibited higher levels of microrna (mir)-145 and mir-221. The upregulation of mir-145 and mir-221 was associated with the enhanced proliferation of periosteal cells and chondrogenic potential, respectively. The present study provided evidence in support for the use of patient-derived exosomes, produced from adScs, for potential chondrogenic regeneration and subsequent amelioration of osteoarthritis.

Exosomes: roles and therapeutic potential in osteoarthritis

“…209 • Promote chondrocytes viability, maintain the balance of anabolism and catabolism via miR-100-5p-mediated mTOR inhibition and autophagy enhancement. 146 • Enhance proliferation and chondrogenic potential of periosteal cells via upregulating miR-145 and miR-221 211 • Down-regulate mitochondrial membrane potential. 208 • promote chondrogenesis in periosteal cells and increase chondrogenic markers 211 • Show the potential anti-inflammatory and chondro-protective effects.…”

“…146 • Enhance proliferation and chondrogenic potential of periosteal cells via upregulating miR-145 and miR-221 211 • Down-regulate mitochondrial membrane potential. 208 • promote chondrogenesis in periosteal cells and increase chondrogenic markers 211 • Show the potential anti-inflammatory and chondro-protective effects. 208,209 • Ameliorate the pathological severity of articular cartilage and partially improve the abnormal gait.…”

Exosomes From Adipose-Derived Stem Cells: The Emerging Roles and Applications in Tissue Regeneration of Plastic and Cosmetic Surgery

“…Furthermore, in the next study, they confirmed that microvesicles and exosomes secreted from ASCs could affect the metabolism of OA chondrocytes by modulating inflammatory and degradative pathways associated with joint destruction (Tofiño-Vian et al, 2018). Zhao et al (2020) separated the patient ASC-exos, which exerted a strong stimulatory effect on chondrocyte migration and proliferation with the upregulation of miR-145 and miR-221 in the model of the inflammation-inflicted oxidative stress. Woo et al also confirmed that human ASC-EVs could potentially protect cartilage from degeneration and could delay cartilage degeneration in OA rat and mouse models.…”

Mesenchymal Stromal Cell Immunology for Efficient and Safe Treatment of Osteoarthritis

“…These changes were likely due to reduced activity of NF-kB and AP-1. Similarly, Zhao et al (2020) reported that AT-MSC-derived exosomes displayed chondroprotective and anti-inflammatory properties. They found that co-culture of AT-MSC-derived exosomes with activated synovial fibroblasts reduced the expression of IL-6 and TNF-α, whereas the expression of IL-10 was enhanced.…”

“…Co-culture with chondrocytes protected from H 2 O 2 -induced apoptosis. Interestingly, treatment with exosomes stimulated chondrogenesis and increased the expression of chondrogenic markers, such as collagen type II and β-catenin (Zhao et al, 2020). More recently, it was evidenced that human AT-MSC-derived EVs increased human OA chondrocyte proliferation and migration, enhanced type II collagen synthesis, and reduced IL-1-mediated expression of key catabolic enzymes, MMP-1, MMP-3, MMP-13, and ADAMTS-5 (Woo et al, 2020).…”