Faculty, Staff and Student Publications
Language
English
Publication Date
12-24-2024
Journal
International Journal of Molecular Sciences
DOI
10.3390/ijms26010016
PMID
39795874
PMCID
PMC11720453
PubMedCentral® Posted Date
12-24-2024
PubMedCentral® Full Text Version
Post-print
Abstract
Pseudoachondroplasia (PSACH), a severe dwarfing condition characterized by impaired skeletal growth and early joint degeneration, results from mutations in cartilage oligomeric matrix protein (COMP). These mutations disrupt normal protein folding, leading to the accumulation of misfolded COMP in chondrocytes. The MT-COMP mouse is a murine model of PSACH that expresses D469del human COMP in response to doxycycline and replicates the PSACH chondrocyte and clinical pathology. The basis for the mutant-COMP pathology involves endoplasmic reticulum (ER) stress signaling through the PERK/eIF2α/CHOP pathway. C/EBP homologous protein (CHOP), in conjunction with a TNFα inflammatory process, upregulates mTORC1, hindering autophagy clearance of mutant COMP protein. Life-long joint pain/degeneration diminishes quality of life, and treatments other than joint replacements are urgently needed. To assess whether molecules that reduce CHOP activity should be considered as a potential treatment for PSACH, we evaluated MT-COMP mice with 50% CHOP (MT-COMP/CHOP
Keywords
Achondroplasia, Femur, Transcription Factor CHOP, Cartilage Oligomeric Matrix Protein, Mice, Transgenic, Arthralgia, Joint Diseases, Chondrocytes, Growth Plate, Cell Death, Mice, Inbred C57BL, Male, Animals, Mice, cartilage oligomeric matrix protein, COMP, autophagy, ASO, CHOP, chondrocyte, ER stress, joint degeneration
Published Open-Access
yes
Recommended Citation
, "Loss of CHOP Prevents Joint Degeneration and Pain in a Mouse Model of Pseudoachondroplasia" (2024). Faculty, Staff and Student Publications. 155.
https://digitalcommons.library.tmc.edu/uthdb_docs/155