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Lookup NU author(s): Dr Matthew Barter, Andrew Butcher, Dr Hui Wang, Dr Dimitra Tsompani, Dr Martin Galler, Ellen Rumsby, Professor David YoungORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022, The Author(s). Elevated pro-inflammatory signalling coupled with catabolic metalloproteinase expression is a common feature of arthritis, leading to cartilage damage, deterioration of the joint architecture and the associated pain and immobility. Countering these processes, histone deacetylase inhibitors (HDACi) have been shown to suppress matrix metalloproteinase (MMP) expression, block cytokine-induced signalling and reduce the cartilage degradation in animal models of the arthritis. In order to establish which specific HDACs account for these chondro-protective effects an HDAC1-11 RNAi screen was performed. HDAC6 was required for both the interleukin (IL)-1 induction of MMP expression and pro-inflammatory interleukin expression in chondrocytes, implicating an effect on NF-κB signalling. Depletion of HDAC6 post-transcriptionally up-regulated inhibitor of κB (IκB), prevented the nuclear translocation of NF-κB subunits and down-regulated NF-κB reporter activation. The pharmacological inhibition of HDAC6 reduced MMP expression in chondrocytes and cartilage collagen release. This work highlights the important role of HDAC6 in pro-inflammatory signalling and metalloproteinase gene expression, and identifies a part for HDAC6 in the NF-κB signalling pathway. By confirming the protection of cartilage this work supports the inhibition of HDAC6 as a possible therapeutic strategy in arthritis.
Author(s): Barter MJ, Butcher A, Wang H, Tsompani D, Galler M, Rumsby EL, Culley KL, Clark IM, Young DA
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Year: 2022
Volume: 12
Issue: 1
Online publication date: 22/04/2022
Acceptance date: 06/04/2022
Date deposited: 12/05/2022
ISSN (electronic): 2045-2322
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41598-022-10518-z
DOI: 10.1038/s41598-022-10518-z
PubMed id: 35459919
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