These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Targeting miR-18a sensitizes chondrocytes to anticytokine therapy to prevent osteoarthritis progression.
    Author: Lian C, Tao T, Su P, Liao Z, Wang X, Lei Y, Zhao P, Liu L.
    Journal: Cell Death Dis; 2020 Nov 03; 11(11):947. PubMed ID: 33144571.
    Abstract:
    Inflammation participates in the development of OA and targeting inflammatory signaling pathways is a potential strategy for OA treatment. IL-1β is one of the most important inflammatory factors to trigger the activation of NF-κB signaling and accelerate OA progression, whereas OA patients could hardly benefit from inhibiting IL-1β in clinic, suggesting the importance to further explore the details of OA inflammation. We here showed that expression of miR-18a in chondrocytes was specifically induced in response to IL-1β in vitro as well as in rat model of OA during which NF-κB signaling was involved, and that nuclear-translocated p65 directly upregulated miR-18a expression at transcriptional level. Further, increased miR-18a mediated hypertrophy of chondrocytes, resulting in OA degeneration, by targeting TGFβ1, SMAD2, and SMAD3 and subsequently leading to repression of TGF-β signaling. And the level of serum miR-18a was positively correlated to severity of OA. Interestingly, other than IL-1β, pro-inflammation cytokines involving TNFα could also remarkably upregulate miR-18a via activating NF-κB signaling and subsequently induce chondrocytes hypertrophy, suggesting a pivotal central role of miR-18a in inflammatory OA progression. Thus, our study revealed a novel convergence of NF-κB and TGF-β signaling mediated by miR-18a, and a novel mechanism underlying inflammation-regulated OA dependent of NF-κB/miR-18a/TGF-β axis. Notably, in vivo assay showed that targeting miR-18a sensitized OA chondrocytes to IL-1β inhibitor as targeting IL-1β and miR-18a simultaneously had much stronger inhibitory effects on OA progression than suppressing IL-1β alone. Therefore, the diagnostic and therapeutic potentials of miR-18a for OA were also revealed.
    [Abstract] [Full Text] [Related] [New Search]