Chondrocyte-specific knockout of Piezo1 and Piezo2 protects against post-traumatic osteoarthritis structural damage and pain in mice

作者：Erica V. Ely, Kristin L. Lenz, Sophie G. Paradi, Seth Ack, Abraham Behrmann, Sarah Dunivan, Lauryn Braxton, Wolfgang Liedtke, Yong Chen, Kelsey H. Collins, Farshid Guilak · 发表于：Arthritis Research & Therapy · 年份：2025 · DOI：10.1186/s13075-025-03620-w · 被引用次数：9 · 研究领域：Erythrocyte Function and Pathophysiology、Osteoarthritis Treatment and Mechanisms、Bone and Joint Diseases

BACKGROUND: Osteoarthritis (OA) is a debilitating joint disease characterized by cartilage degeneration, synovial inflammation, and bone remodeling, with limited therapeutic options targeting the underlying pathophysiology. Mechanosensitive ion channels Piezo1 and Piezo2 play crucial roles in chondrocyte responses to mechanical stress, mediating mechanotransduction pathways that influence chondrocyte survival, matrix production, and inflammatory signaling, but their distinct contributions to OA pathogenesis remain unclear. METHODS: Using inducible, chondrocyte-specific Aggrecan-Cre (Acan) mice, we investigated Piezo1, Piezo2, and combined Piezo1/2 conditional knockouts (cKOs) using the destabilization of the medial meniscus (DMM) model of post-traumatic OA in male and female mice. Pain and behavioral assessments were conducted at four time points to evaluate OA progression, while cartilage damage, bone remodeling, and synovial inflammation were assessed at the final endpoint of 28 weeks. Statistical analyses included one-way and two-way ANOVA with Tukey's multiple comparison test. RESULTS: Piezo1 cKO delayed pain onset but ultimately exacerbated cartilage degradation and synovitis, emphasizing its dual role in protective and pathogenic mechanotransduction. While the Piezo2 cKO reduced pain and preserved activity, it failed to protect cartilage. Notably, Piezo1/2 cKO provided the greatest protection against cartilage degeneration, synovitis, and pain. Micro-computed tomography...