PTHrP buffers Wnt/β-catenin activity through a PKC-ζ involved negative feedback loop to maintain articular cartilage homeostasis and attenuate osteoarthritis.

ABSTRACT:

Background

Osteoarthritis (OA) is the most common joint disease worldwide and a leading cause of disability. The Wnt/β-catenin cascade is essential in articular cartilage development and homeostasis. Interruption of β-catenin (either overexpression or inhibition) leads to cartilage degeneration. However, the mechanism for stabilizing Wnt/β-catenin remains unclear.

Methods

We established the mouse destabilization of the medial meniscus (DMM) OA model and analyzed the clinical specimens to detect Wnt/β-catenin and PTHrP. The chondrocytes were isolated and treated with various cytokines including Wnt3a, Ihh, IL-1β, and PTHrP to reveal the molecular mechanism. Epigenetic and bioinformatic analyses were conducted to screen the key genes for the PTHrP regulation, and an Adeno-asso

SUBMITTER: Tong WX 

PROVIDER: S-EPMC12304701 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature