Attenuation of experimental osteoarthritis with human adipose-derived mesenchymal stem cell therapy: inhibition of the pyroptosis in chondrocytes

• Published in: Inflammation research 2023, Vol.72 (1), p.89-105
• Main Authors: Xu, Liang, Zhang, Feng, Cheng, Gang, Yuan, Xiaoyang, Wu, Yujiao, Wu, Huaxun, Wang, Qingtong, Chen, Jingyu, Kuai, Jiajie, Chang, Yan, Wei, Wei, Yan, Shangxue
• Format: Article
• Language: English
• Subjects: Allergology; Animals; Arthritis; Biomedical and Life Sciences; Biomedicine; Cell morphology; Cell therapy; Cells, Cultured; Chondrocytes; Chondrocytes - metabolism; Cytology; Dermatology; Electron microscopy; Histopathology; Humans; Immunofluorescence; Immunohistochemistry; Immunology; Inflammation; Interleukin 18; Joint diseases; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Microscopy; Neurology; Original Research; Osteoarthritis; Osteoarthritis - metabolism; Pharmacology/Toxicology; Proteins; Pyroptosis; Rats; Rats, Sprague-Dawley; Receptors, Tumor Necrosis Factor, Type I; Rheumatology; Safranin-O; Scanning electron microscopy; Signal transduction; Signaling; Staining; Stem cell transplantation; Stem cells; Transmission electron microscopy; Tumor necrosis factor receptors; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Ultrastructure
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-022-01655-2

Aim To explore the role and mechanism of human adipose-derived mesenchymal stem cells (hAD-MSCs) in the treatment of osteoarthritis (OA). Methods OA hulth model of Sprague Dawley (SD) rats and 20 ng/ml TNF-α treated chondrocytes were used as models of OA in vivo and in vitro, respectively. hAD-MSCs were administrated in the articular cavity by injection in vivo and co-cultured with chondrocytes using transwell in vitro. Haematoxylin and eosin staining and Safranin-O/Fast green staining were performed to detect tissue destruction and histopathology. Scanning electron microscopy and transmission electron microscopy were used to observe the ultrastructure of chondrocytes. The pyroptosis signaling pathway-related proteins were detected by immunohistochemistry, immunofluorescence, qRT-PCR and Western blot. And small interference technology was used to study the mechanism in depth. Results hAD-MSCs could delay the development of rat OA, improve the pathological changes of joints, inhibit the expression of NLRP3, Caspase1, GSDMD and TNFR1. In vitro, the expression of pyroptosis signal proteins in chondrocytes was significantly elevated when stimulated with TNF-α, the level of inflammatory factors such as IL-1β, IL-18 was increased, and the cell morphology was significantly destroyed. While co-cultured with hAD-MSCs, these syndromes were reversed. Knockout of TNFR1 also returned the upregulation of pyroptosis signals which caused by TNF-α. Conclusion These results demonstrated that hAD-MSCs could inhibit pyroptosis signaling pathway of chondrocytes induced by TNF-α, which have raised our understanding of the role of hAD-MSCs as promising therapy for the management of OA.