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Fig. 2 | Arthritis Research & Therapy

Fig. 2

From: Senescence in osteoarthritis: from mechanism to potential treatment

Fig. 2

The effects of mechanical stress on chondrocytes. Under mechanical stress conditions, Piezo1 and TRPV4 channels are activated, leading to Ca2+ influx into the cytoplasmand triggering endoplasmic reticulum stress and mitochondrial dysfunction. mtROS and mtDNA are released from damaged mitochondria, which results in DNA damage, active catabolism and cartilage degeneration. NF-κB is usually activated during senescence and promotes SASP factor transcription. Mechanical stress inhibits FBXW7-dependent MKK7 degradation, which leads to JNK pathway activation and cellular senescence. JNK also has anti-senescence effect by regulating p16. The Rac1-ROS pathway participates in NF-κB activation under mechanical stress and promotes the production of gremlin-1. Gremlin-1 in turn activates NF-κB via VEGF2 in an autocrine or paracrine manner. TRPV4, transient receptor potential vanilloid 4; mtROS, mitochondrial reactive oxygen species; NF-κB, nuclear factor kappa-B; SASP, senescence-associated secretory phenotype; FBXW7, F-box and WD repeat domain containing 7; MKK7, mitogen-activated protein kinase kinase 7; JNK, mitogen-activated protein kinase; Rac1, Ras-related C3 botulinum toxin substrate 1; VEGF2, vascular endothelial growth factor 2

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