The E3 ubiquitin ligase Itch limits the progression of post-traumatic osteoarthritis in mice by inhibiting macrophage polarization.

ABSTRACT:

Objective

Osteoarthritis (OA) is characterized by articular cartilage loss, associated with synovial inflammation. We recently reported increased pro-inflammatory macrophages in murine post-traumatic OA (PTOA) joints, and blockade of the ubiquitin-proteasome system alleviates PTOA progression. However, the mechanisms whereby protein ubiquitination influences PTOA pathology are not well studied. We hypothesized that loss of the negative regulator of inflammation, E3 ligase Itch, in macrophages contributes to joint OA tissue damage by promoting pro-inflammatory polarization of macrophages.

Methods

Mice deficient Itch in macrophages (MΔItch) were generated by crossing Itch^fl/fl mice with LysM-Cre mice. PTOA surgery was performed on global Itch knockout, Itch^-/-<

SUBMITTER: Lin X 

PROVIDER: S-EPMC8319075 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature