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Article

ER Stress in ERp57 Knockout Knee Joint Chondrocytes Induces Osteoarthritic Cartilage Degradation and Osteophyte Formation

1
Institute of Physiological Chemistry and Pathobiochemistry, Waldeyerstraße 15, 48149 Muenster, Germany
2
Institute of Musculoskeletal Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building D3, 48149 Muenster, Germany
3
Center for Applied Tissue Engineering and Regenerative Medicine-CANTER, Munich University of Applied Sciences, 80335 Munich, Germany
4
Center for Nanoscience-CeNS, 80335 Munich, Germany
5
Department for Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), University Hospital, LMU Munich, 80335 Munich, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Riko Nishimura
Int. J. Mol. Sci. 2022, 23(1), 182; https://doi.org/10.3390/ijms23010182
Received: 15 November 2021 / Revised: 14 December 2021 / Accepted: 22 December 2021 / Published: 24 December 2021
(This article belongs to the Special Issue Bone and Cartilage Biology)
Ageing or obesity are risk factors for protein aggregation in the endoplasmic reticulum (ER) of chondrocytes. This condition is called ER stress and leads to induction of the unfolded protein response (UPR), which, depending on the stress level, restores normal cell function or initiates apoptotic cell death. Here the role of ER stress in knee osteoarthritis (OA) was evaluated. It was first tested in vitro and in vivo whether a knockout (KO) of the protein disulfide isomerase ERp57 in chondrocytes induces sufficient ER stress for such analyses. ER stress in ERp57 KO chondrocytes was confirmed by immunofluorescence, immunohistochemistry, and transmission electron microscopy. Knee joints of wildtype (WT) and cartilage-specific ERp57 KO mice (ERp57 cKO) were analyzed by indentation-type atomic force microscopy (IT-AFM), toluidine blue, and immunofluorescence/-histochemical staining. Apoptotic cell death was investigated by a TUNEL assay. Additionally, OA was induced via forced exercise on a treadmill. ER stress in chondrocytes resulted in a reduced compressive stiffness of knee cartilage. With ER stress, 18-month-old mice developed osteoarthritic cartilage degeneration with osteophyte formation in knee joints. These degenerative changes were preceded by apoptotic death in articular chondrocytes. Young mice were not susceptible to OA, even when subjected to forced exercise. This study demonstrates that ER stress induces the development of age-related knee osteoarthritis owing to a decreased protective function of the UPR in chondrocytes with increasing age, while apoptosis increases. Therefore, inhibition of ER stress appears to be an attractive therapeutic target for OA. View Full-Text
Keywords: cartilage; ER stress; osteoarthritis; apoptosis; osteophytes cartilage; ER stress; osteoarthritis; apoptosis; osteophytes
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MDPI and ACS Style

Rellmann, Y.; Eidhof, E.; Hansen, U.; Fleischhauer, L.; Vogel, J.; Clausen-Schaumann, H.; Aszodi, A.; Dreier, R. ER Stress in ERp57 Knockout Knee Joint Chondrocytes Induces Osteoarthritic Cartilage Degradation and Osteophyte Formation. Int. J. Mol. Sci. 2022, 23, 182. https://doi.org/10.3390/ijms23010182

AMA Style

Rellmann Y, Eidhof E, Hansen U, Fleischhauer L, Vogel J, Clausen-Schaumann H, Aszodi A, Dreier R. ER Stress in ERp57 Knockout Knee Joint Chondrocytes Induces Osteoarthritic Cartilage Degradation and Osteophyte Formation. International Journal of Molecular Sciences. 2022; 23(1):182. https://doi.org/10.3390/ijms23010182

Chicago/Turabian Style

Rellmann, Yvonne, Elco Eidhof, Uwe Hansen, Lutz Fleischhauer, Jonas Vogel, Hauke Clausen-Schaumann, Attila Aszodi, and Rita Dreier. 2022. "ER Stress in ERp57 Knockout Knee Joint Chondrocytes Induces Osteoarthritic Cartilage Degradation and Osteophyte Formation" International Journal of Molecular Sciences 23, no. 1: 182. https://doi.org/10.3390/ijms23010182

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