Abstract
BackgroundCartilage defects account for substantial economic and humanistic burdens and pose a significant clinical problem. The efficacy of clinical approaches to cartilage repair is often inadequate, in part, owing to the restricted proliferative capacity of chondrocytes. Molecules have the capacity to promote the differentiation of multipotent mesenchymal stem cells into chondrocytes and may also gain the ability to repair the damaged cartilage.ObjectiveThis study aimed to investigate the role of Atsttrin (progranulin-derived engineered protein) in cartilage repair as well as the signaling pathway involved.MethodsPrimary and mesenchymal stem cell lines were used for the micromass culture. A murine cartilage defect model was used to determine the role of Atsttrin in cartilage repair in vivo. Real-time polymerase chain reaction and Western blot analysis were used to monitor the effect of Atsttrin on the transcriptional and protein levels, respectively, of key anabolic and catabolic signaling molecules.ResultsAtsttrin stimulated chondrogenesis in vitro and accelerated cartilage repair in vivo. In addition, Atsttrin-mediated cartilage repair occurred primarily through tumor necrosis factor receptor 2-initiated Akt signaling and downstream JunB transcription factor.ConclusionAtsttrin might serve as a promising therapeutic modality for cartilage regeneration.
Highlights
Articular cartilage diseases affect more than 273 million of adults across the world (Helmick et al, 2008; Lawrence et al, 2008; Krishnan and Grodzinsky, 2018)
Given the stimulatory effect of PGRN on chondrogenesis, the present study first sought to investigate whether PGRNderivative Atsttrin could induce chondrogenesis
Atsttrin-mediated cartilage repair was significantly reduced in TNFR2–/– mice compared with TNFR1–/– mice. These results indicated that Atsttrin-mediated cartilage repair depended mainly on the presence of TNFR2
Summary
Articular cartilage diseases affect more than 273 million of adults across the world (Helmick et al, 2008; Lawrence et al, 2008; Krishnan and Grodzinsky, 2018). Damage to the articular cartilage can result in potentially crippling symptoms, such as swelling, pain and decreased mobility, and, if left untreated, osteoarthritis (OA). Even minor cartilage injuries may lead to persistent tissue damage and eventual OA. Improved corrective approaches for cartilage damage are critical to limiting humanistic and financial losses incurred following cartilage injury. Cartilage defects account for substantial economic and humanistic burdens and pose a significant clinical problem. The efficacy of clinical approaches to cartilage repair is often inadequate, in part, owing to the restricted proliferative capacity of chondrocytes. Molecules have the capacity to promote the differentiation of multipotent mesenchymal stem cells into chondrocytes and may gain the ability to repair the damaged cartilage
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