Ipriflavone attenuates the degeneration of cartilage by blocking the Indian hedgehog pathway.

ABSTRACT:

Background

To determine if ipriflavone, a novel and safe inhibitor of Indian hedgehog (Ihh) signaling, can attenuate cartilage degeneration by blocking the Ihh pathway.

Methods

Human chondrocytes were used to evaluate Ihh signaling, cell proliferation, apoptosis, gene, and protein expression of chondrocytes by cell proliferation and apoptosis assays, real-time qPCR, and Western blotting at 48?h after ipriflavone treatment. Human cartilage explants were further used to validate the cell culture results. The effects of ipriflavone on cartilage degeneration in vivo were assessed using the rat ACLT OA model. Two-month-old male SD rats were randomized into 3 groups (n =?75): (1) sham, (2) ACLT alone, and (3) ACLT+ ipriflavone. Ipriflavone was administered intragastrically at 24?h after ACLT for 6?weeks. The extent of OA progression was evaluated by the OARSI score and immunohistochemistry at 12?weeks after surgery. The Ihh signaling pathway and OA-related genes were quantified by real-time PCR.

Results

Cell proliferation in the cells treated with ipriflavone was increased to 36.40%?±?1.32% (5??M) and 28.54%?±?0.74% (10??M) from 11.99%?±?0.35% (DMSO) (P ConclusionsCatabolic genes were disrupted by blocking the Ihh pathway. This finding suggests that disruption of Ihh signaling with ipriflavone provides chondral protection in rat posttraumatic OA.

SUBMITTER: Guo L 

PROVIDER: S-EPMC6498579 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature