Cartilage degeneration pathways

Cartilage degeneration pathways encompass interconnected signaling networks that disrupt cartilage homeostasis in osteoarthritis, including overactivation of Wnt/β-catenin signaling, imbalanced TGF-β pathways, inflammatory cascades (e.g., JAK2/STAT3), and upregulation of matrix-degrading enzymes such as MMP13 and ADAMTS-5; therapeutic research targets these axes with Wnt pathway modulators (e.g., lorecivivint), protease inhibitors, and pathway-directed agents to slow matrix catabolism, support chondrogenesis, and modulate chondrocyte survival and autophagy, though achieving efficacy without impairing physiological cartilage and bone processes remains a key challenge.

Other names

cartilage catabolic pathwaysosteoarthritic cartilage signalingOA cartilage degeneration signalingpathways of cartilage degradation

Inhibition of Wnt/β-catenin–related transcriptional programs to reduce catabolic enzymes and support chondrogenesis (e.g., Lorecivivint via CLK2/DYRK1A; XAV-939 tankyrase inhibition stabilizing AXIN and suppressing β-catenin); Direct inhibition of matrix-degrading enzymes (MMP13, ADAMTS-5) to slow extracellular matrix breakdown; Modulation of JAK2/STAT3 to reduce chondrocyte apoptosis, promote ECM anabolism, and influence autophagy