Platelet-Derived Exosomes Alleviate Knee Osteoarthritis by Attenuating Cartilage Degeneration and Subchondral Bone Loss

Abstract

Background: Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease among the aged population. However, current treatments for OA are limited to alleviating symptoms, with no therapies that prevent and regenerate cartilage deterioration. Purpose: To assess the effects of platelet-derived exosomes (Plt-exos) on OA and then to explore the potential molecular mechanism. Study Design: Controlled laboratory study. Methods: Exosomes derived from human apheresis platelets were isolated and identified. The effects of Plt-exos in protecting chondrocytes under interleukin 1β stimulation were evaluated by analyzing the proliferation and migration in human primary chondrocytes. RNA sequencing was later performed in vitro for primary chondrocytes to reveal the underlying mechanisms of Plt-exo treatment. Anterior cruciate ligament transection was used to construct an OA mice model, and intra-articular injection of Plt-exos was given once a week for 6 weeks. Mice were sacrificed 4 weeks after the last injection. Histologic and immunohistochemistry staining and micro–computed tomography analysis were performed to assess alterations of articular cartilage and subchondral bone. Results: Plt-exos significantly promoted proliferation and migration of chondrocytes within a dose-dependent manner, as well as dramatically promoted cartilage regeneration and attenuated abnormal tibial subchondral bone remodeling, thus slowing the progression of OA. After being treated with Plt-exos, 1797 genes were differentially expressed in chondrocytes (923 upregulated and 874 downregulated genes). Functional enrichment results and hub genes were mainly involved in anti-inflammatory effects, mediating cell adhesion, stimulating cartilage repair, promoting anabolism, and inhibiting catabolism. Conclusion: Our results demonstrated that Plt-exos promoted chondrocyte proliferation and migration in vitro, as well as attenuated cartilage degeneration, improved the microarchitecture of subchondral bone, and retarded OA progression in vivo. Clinical Relevance: Our study illustrated that the administered Plt-exos could alleviate knee OA by attenuating cartilage degeneration and subchondral bone loss, possibly serving as a novel promising treatment for OA in the future.

HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures

“…Compared with MSCs, EVs have advantages such as simple storage and transportation conditions, no tumorigenicity, no risk of disease transmission, and no risk of immune rejection [49,50]. At present, the main exosomes derived for the treatment of cartilage injury include infrapatellar fat pad MSCs [51], synovial MSCs [52], human urine-derived stem cells [53], cartilage endplate stem cells [54], platelets [55], human anatomical MSCs [56], and Wharton's jelly MSCs [57]. However, only HWJMSC-EVs are reported to contain the protein ITGB1, as confirmed in our experiments.…”

The Role of Extracellular Vesicles in the Pathogenesis and Treatment of Rheumatoid Arthritis and Osteoarthritis

“…Nevertheless, EVs secreted by different cells have also been found to have immunomodulatory properties. For instance, platelet-derived exosomes demonstrated significant positive effects on chondrocytes, as well as in OA animal models [161]. Mir-126-3p has been found to suppress chondrocyte inflammation and induce proliferation.…”

Exosomes: The New Kid on the Block in Orthobiologics

“…The American Journal of Sports Medicine has published many preclinical (animal) and human clinical papers in recent years on the role of MSCs in soft tissue repair, and more recently, the journal has published preclinical studies evaluating exosomes. 2,18 The interest, hype, and aggressive marketing that we have seen related to ''stem cells'' is now being repeated with exosomes/EVs. Although there are currently no approved exosome products in orthopaedics, an online search reveals numerous examples of inappropriate and indiscriminate marketing of ''exosome therapies'' by commercial entities, and our patients are beginning to ask about these products based on this widespread advertising.…”