Loss of CHOP Prevents Joint Degeneration and Pain in a Mouse Model of Pseudoachondroplasia
Abstract
:1. Introduction
2. Results
2.1. Loss of CHOP in MT-COMP Mice Does Not Improve Femur Length
2.2. Reduction of CHOP Partially Normalizes COMP Localization in the Growth Plate
2.3. Joint Health Is Preserved with Loss of CHOP
2.4. Pain Mitigation Is Associated with the Absence or Reduction of CHOP in MT-COMP Mice
2.5. Articular Chondrocyte Death and Markers of Pathologic Processes That Lead to Cell Death Are Reduced in the Absence or Reduction of CHOP
2.6. Loss or Reduction of CHOP in MT-COMP Lessens Inflammation and Downstream Molecules in Articular Chondrocytes
3. Discussion
4. Materials and Methods
4.1. Bigenic Mice
4.2. Mutant COMP Induction
4.3. CHOP ASO Treatment
4.4. Immunohistochemistry
4.5. Limb Length Measurements
4.6. Grooming Assessments
4.7. Joint Degeneration Scoring
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Comparison | p Value at Time Points in Weeks (wks) | ||||||
---|---|---|---|---|---|---|---|
8 wk | 12 wk | 16 wk | 20 wk | 24 wk | 30 wk | 36 wk | |
Control vs. MT-COMP | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 |
Control vs. MT-COMP/CHOP−/− | 0.292 | 0.716 | 0.408 | 0.056 | 0.598 | 1.000 | 0.814 |
Control vs. MT-COMP/CHOP−/+ | 0.079 | 0.999 | 0.111 | 0.294 | - | - | - |
MT-COMP vs. Control | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 |
MT-COMP vs. MT-COMP/CHOP−/− | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | 0.003 |
MT-COMP vs. MT-COMP/CHOP−/+ | <0.001 | <0.001 | <0.001 | 0.007 | - | - | - |
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Hecht, J.T.; Veerisetty, A.C.; Hossain, M.G.; Patra, D.; Carrer, M.; Chiu, F.; Relic, D.; Jafar-nejad, P.; Posey, K.L. Loss of CHOP Prevents Joint Degeneration and Pain in a Mouse Model of Pseudoachondroplasia. Int. J. Mol. Sci. 2025, 26, 16. https://doi.org/10.3390/ijms26010016
Hecht JT, Veerisetty AC, Hossain MG, Patra D, Carrer M, Chiu F, Relic D, Jafar-nejad P, Posey KL. Loss of CHOP Prevents Joint Degeneration and Pain in a Mouse Model of Pseudoachondroplasia. International Journal of Molecular Sciences. 2025; 26(1):16. https://doi.org/10.3390/ijms26010016
Chicago/Turabian StyleHecht, Jacqueline T., Alka C. Veerisetty, Mohammad G. Hossain, Debabrata Patra, Michele Carrer, Frankie Chiu, Dorde Relic, Paymaan Jafar-nejad, and Karen L. Posey. 2025. "Loss of CHOP Prevents Joint Degeneration and Pain in a Mouse Model of Pseudoachondroplasia" International Journal of Molecular Sciences 26, no. 1: 16. https://doi.org/10.3390/ijms26010016
APA StyleHecht, J. T., Veerisetty, A. C., Hossain, M. G., Patra, D., Carrer, M., Chiu, F., Relic, D., Jafar-nejad, P., & Posey, K. L. (2025). Loss of CHOP Prevents Joint Degeneration and Pain in a Mouse Model of Pseudoachondroplasia. International Journal of Molecular Sciences, 26(1), 16. https://doi.org/10.3390/ijms26010016