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MicroRNA-613 alleviates IL-1?-induced injury in chondrogenic CHON-001 cells by targeting fibronectin 1

ABSTRACT: Background: Osteoarthritis (OA) is an aging-related chronic degenerative joint disease. A number of miRNAs have been found to be involved in the development of OA, but the role of miR-613 in OA remains unclear. Thus, this study aimed to investigate the role of miR-613 during the progression of OA. Methods: CHON-001 cells were transfected with miR-613 agonist for 48 h, and then exposed to 10 ng/mL IL-1? for 24 h. Cell viability, cell proliferation and cell apoptosis in CHON-001 cells were assessed by CCK-8, immunofluorescence, and flow cytometry assays, respectively. In addition, the dual luciferase reporter system assay was used to determine the interaction of miR-613 and fibronectin 1 in CHON-001 cells. Results: The level of miR-613 was significantly decreased in IL-1?-treated CHON-001 cells. Overexpression of miR-613 markedly inhibited IL-1?-induced apoptosis in CHON-001 cells. In addition, upregulation of miR-613 obviously alleviated IL-1?-induced inflammatory response and cartilage matrix degradation in CHON-001 cells. Meanwhile, fibronectin 1 was identified as a direct binding target of miR-613 in CHON-001 cells. Overexpression of miR-613 alleviated IL-1?-induced injury in CHON-001 cells via downregulating the expression of fibronectin 1. Furthermore, overexpression of miR-613 alleviated cartilage degradation, and reduced OARSI scores and subchondral bone thickness in a mouse model of OA. Conclusion: Our data indicated that overexpression of miR-613 could inhibit IL-1?-induced injury in CHON-001 cells via decreasing the level fibronectin 1 in vitro, and alleviate the symptoms of OA in vivo. Therefore, miR-613 might be a potential therapeutic option for the treatment of OA.

SUBMITTER: Xiao P

PROVIDER: S-EPMC7540165 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:Interleukin-1β (IL-1β) is one of the most potent pro-inflammatory cytokines implicated in a wide range of autoinflammatory, autoimmune, infectious, and degenerative diseases. Therefore, many researchers have focused on developing therapeutic molecules that inhibit IL-1β-IL-1 receptor 1 (IL-1R1) interaction for the treatment of IL-1-related diseases. Among IL-1-related diseases, osteoarthritis (OA), is characterized by progressive cartilage destruction, chondrocyte inflammation, and extracellular matrix (ECM) degradation. Tannic acid (TA) has been proposed to have multiple beneficial effects, including anti-inflammatory, anti-oxidant, and anti-tumor activities. However, it is unclear whether TA plays a role in anti-IL-1β activity by blocking IL-1β-IL-1R1 interaction in OA. In this study, we report the anti-IL-1β activity of TA in the progression of OA in both in vitro human OA chondrocytes and in vivo rat OA models. Herein, using-ELISA-based screening, natural compound candidates capable of inhibiting the IL-1β-IL-1R1 interaction were identified. Among selected candidates, TA showed hindering IL-1β-IL-1R1 interaction by direct binding to IL-1β using surface plasmon resonance (SPR) assay. In addition, TA inhibited IL-1β bioactivity in HEK-Blue IL-1-dependent reporter cell line. TA also inhibited IL-1β-induced expression of inducible nitric oxide synthase (NOS2), cyclooxygenase-2 (COX-2), IL-6, tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and prostaglandin E2 (PGE2) in human OA chondrocytes. Moreover, TA downregulated IL-1β-stimulated matrix metalloproteinase (MMP)3, MMP13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)4, and ADAMTS5, while upregulating collagen type II (COL2A1) and aggrecan (ACAN). Mechanistically, we confirmed that TA suppressed IL-1β-induced MAPK and NF-κB activation. The protective effects of TA were also observed in a monosodium iodoacetamide (MIA)-induced rat OA model by reducing pain and cartilage degradation and inhibiting IL-1β-mediated inflammation. Collectively, our results provide evidence that TA plays a potential role in OA and IL-1β-related diseases by hindering IL-1β-IL-1R1 interaction and suppressing IL-1β bioactivity.

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MicroRNA-613 alleviates IL-1?-induced injury in chondrogenic CHON-001 cells by targeting fibronectin 1

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