Stimulation of nuclear receptor REV-ERBs alleviates monosodium iodoacetate-induced osteoarthritis pathology of mice and the induction of inflammatory molecules expression in primary cultured chondrocytes

Hashizume Hiroki

Motonari Hatsune

Yamamoto Kenta

Nakamura Yoki

Hisaoka-Nakashima Kazue

Morioka Norimitsu

International Immunopharmacology

Because inflammation in chondrocytes contributes to the induction of osteoarthritis (OA), regulation of their activity is essential. A previous study showed that stimulation of the reverse erythroblastosis virus (REV-ERB) nuclear receptors in spinal glial cells elicits anti-inflammatory and antinociception effects in animal models of chronic pain. However, the involvement of REV-ERBs in chondrocyte functions and OA pathologies remains to be elucidated. In the current study, we found that pretreatment with the REV-ERB agonist SR9009 significantly blocked the increases in inflammatory molecules [(matrix metalloproteinase (MMP) 3, MMP9, and MMP13] and cytokines (interleukin-1β and tumor necrosis factor) in primary cultured chondrocytes following treatment with lipopolysaccharide. Furthermore, repeated intra-articular treatment with SR9009 significantly prevented monosodium iodoacetate-induced mechanical hypersensitivity and tended to partially reduce knee joint damage in mice. In conclusion, our findings suggest that REV-ERBs have a critical role in alleviating nociceptive hypersensitivity in OA pathologies by negatively regulating inflammation in chondrocytes.

REV-ERBs

Chronic pain

Chondrocyte

Osteoarthritis

Lipopolysaccharide

Monosodium iodoacetate

英語

Elsevier

© 2023. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/

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[DOI] https://doi.org/10.1016/j.intimp.2023.111349 ～の異版である