Early Resveratrol Treatment Mitigates Joint Degeneration and Dampens Pain in a Mouse Model of Pseudoachondroplasia (PSACH).

ABSTRACT: Pseudoachondroplasia (PSACH), a severe dwarfing condition associated with early-onset joint degeneration and lifelong joint pain, is caused by mutations in cartilage oligomeric matrix protein (COMP). The mechanisms underlying the mutant-COMP pathology have been defined using the MT-COMP mouse model of PSACH that has the common D469del mutation. Mutant-COMP protein does not fold properly, and it is retained in the rough endoplasmic reticulum (rER) of chondrocytes rather than being exported to the extracellular matrix (ECM), driving ER stress that stimulates oxidative stress and inflammation, driving a self-perpetuating cycle. CHOP (ER stress signaling protein) and TNFα inflammation drive high levels of mTORC1 signaling, shutting down autophagy and blocking ER clearance, resulting in prematu

SUBMITTER: Hecht JT 

PROVIDER: S-EPMC10605626 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature