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Updated: Jul 21, 2025

A Reproducible Cartilage Impact Model to Generate Post-Traumatic Osteoarthritis in the Rabbit
Published on: November 21, 2023
TRPV4-mediated mitochondrial dysfunction induces pyroptosis and cartilage degradation in osteoarthritis via the
Zijian Yan1, Zili He1, Hongyi Jiang1
1Department of Orthopaedics Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Abstract:
Osteoarthritis (OA) is an age-related chronic degenerative disease with complex pathophysiological mechanisms. Accumulating evidence indicates that nod-like receptor pyrin domain 3 (NLRP3) inflammasome-mediated pyroptosis of chondrocytes plays a crucial role in the OA progression. Transient Receptor Potential Vanilloid 4 (TRPV4), described as a calcium-permeable cation channel, isassociated with proinflammatory factors and pyroptosis. In this study, we studied the potential functions of TRPV4 in chondrocyte pyroptosis and cartilage degradation. We found that lipopolysaccharides(LPS)-induced mitochondrial reactive oxygen species (mtROS) accumulation aggravated chondrocyte pyroptosis and cartilage degeneration. TRPV4 induces dynamin-related protein 1 (Drp1) mitochondrial translocation through the Ca2+-calmodulin-dependent protein kinase II (CaMKII) signaling pathway, which subsequently caused the mitochondrial dysfunction (e.g., mPTP over opening; Δψm depolarization; ATP production decreased; mtROS accumulation), pyroptosis and extracellular matrix (ECM) degradation through hexokinase 2 (HK2) dissociation from mitochondrial membrane. Moreover, TRPV4 inhibition reversed Drp1-involved chondrocyte pyroptosis and cartilage degeneration in the anterior cruciate ligament transection (ACLT) mouse model. Our findings revealed the internal mechanisms underlying TRPV4 regulation in chondrocytes and its intrinsic therapeutic efficacy for OA.
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