RRC ID 67517
Author Kaihara K, Nakagawa S, Arai Y, Inoue H, Tsuchida S, Fujii Y, Kamada Y, Kishida T, Mazda O, Takahashi K.
Title Sustained Hypoxia Suppresses Joint Destruction in a Rat Model of Rheumatoid Arthritis via Negative Feedback of Hypoxia Inducible Factor-1α.
Journal Int J Mol Sci
Abstract Hypoxia inducible factor (HIF)-1α has been implicated in the pathogenesis of rheumatoid arthritis (RA). HIF-1α, which is expressed in hypoxia, is reversely suppressed in sustained hypoxia. Here, we investigated the inhibitory effect of hypoxia on arthritis by controlling HIF-1α. Rheumatoid fibroblast-like synoviocyte MH7A cells were cultured in a hypoxic incubator for up to 72 h to evaluate the expression of HIF-1. Furthermore, collagen-induced arthritis (CIA) model rats were maintained under 12% hypoxia in a hypoxic chamber for 28 days to evaluate the effect on arthritis. In MH7A cells, HIF-1α protein level increased at 3 h, peaked at 6 h, and subsequently decreased in a time-dependent manner. The transcription of pro-inflammatory cytokines increased at 1 h; however, they decreased after 3 h (p < 0.05). Deferoxamine-mediated activation of HIF-1α abolished the inhibitory effect of sustained hypoxia on pro-inflammatory cytokines. In the rat CIA model, the onset of joint swelling was delayed and arthritis was suppressed in the hypoxia group compared with the normoxia group (p < 0.05). Histologically, joint destruction was suppressed primarily in the cartilage. Thus, sustained hypoxia may represent a new safe, and potent therapeutic approach for high-risk patients with RA by suppressing HIF-1α expression.
Volume 22(8)
Published 2021-4-9
DOI 10.3390/ijms22083898
PII ijms22083898
PMID 33918929
PMC PMC8068944
MeSH Animals Arthritis, Rheumatoid / etiology* Arthritis, Rheumatoid / metabolism* Arthritis, Rheumatoid / pathology Biomarkers Cell Hypoxia Cells, Cultured Cytokines / genetics Cytokines / metabolism Disease Susceptibility Fibroblasts / metabolism Gene Expression Hypoxia / genetics Hypoxia / metabolism* Hypoxia / pathology Hypoxia-Inducible Factor 1, alpha Subunit / genetics Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Inflammation Mediators / metabolism Rats Synoviocytes / metabolism Synoviocytes / pathology
IF 4.556
Human and Animal Cells MH7A(RCB1512)