Abstract
This study aimed to investigate the potential roles of circRNAs in regulating osteoarthritis (OA)-related ghrelin synthesis, autophagy induction, and the relevant molecular mechanisms. Results showed that Col2a1, Acan, ghrelin, and autophagy-related markers expression were downregulated, while matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) expressions increased in both IL-1β-induced rat chondrocytes and cartilage tissues of OA rats. A total of 130 circRNAs and 731 mRNAs were differentially expressed in IL-1β-induced rat chondrocytes. Among them, we found that circPan3 expression was significantly decreased in both cellular and animal OA models. CircPan3 directly targeted miR-667-5p. CircPan3 overexpression promoted Col2a1, Acan, ghrelin, beclin 1, and LC3-II expression but reduced MMP13 and ADAMTS5 expression in rat chondrocytes, whereas overexpression of miR-667-5p exhibited opposite effects on the above markers. Furthermore, we found that miR-667-5p bound directly to the 3′-UTR sequence of ghrelin gene. Moreover, the circPan3-induced alterations in chondrocytes were antagonized by miR-667-5p overexpression. Taken together, our findings demonstrate that circPan3 promotes ghrelin synthesis and chondrocyte autophagy via targeting miR-667-5p, protecting against OA injury. This study provided experimental evidence that circPan3/miR-667-5p/ghrelin axis might serve as targets of drug development for the treatment of OA.
Highlights
Osteoarthritis (OA) is a common chronic joint disease characterized by articular cartilage degeneration and subsequent destruction of cartilage and bone
Osteoarthritis is a common joint disease characterized by the dysregulation of chondrocytes and the decrease in extracellular matrix components, its’ pathogenesis is closely associated with chondrocyte autophagy, and ghrelin prevented articular cartilage matrix destruction in human chondrocytes (Zhang et al, 2015; Zou et al, 2016; Liu et al, 2018; Qu et al, 2018; Yu and Zhao, 2019)
This study showed that ghrelin synthesis and autophagy were decreased in both cellular and rat OA models
Summary
Osteoarthritis (OA) is a common chronic joint disease characterized by articular cartilage degeneration and subsequent destruction of cartilage and bone. The Col-II and Acan contents in the articular cartilages were significantly decreased mainly due to abnormal chondrocytes, while the secretion of cartilage-degrading metalloproteinases (MMP13 and ADAMTS5) was elevated (Xie et al, 2017; Lambova and Müller-Ladner, 2018). These abnormal catabolic processes are mainly induced by excessive generation of interleukin-1β (IL1β) and tumor necrosis factor alpha (TNF-α). The molecular mechanisms underlying the development of OA remain poorly unknown
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