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Role of hypoxia-mediated pyroptosis in the development of extending knee joint contracture in rats.
- Source :
-
European journal of medical research [Eur J Med Res] 2024 May 27; Vol. 29 (1), pp. 298. Date of Electronic Publication: 2024 May 27. - Publication Year :
- 2024
-
Abstract
- Joint contracture is one of the common diseases clinically, and joint capsule fibrosis is considered to be one of the most important pathological changes of joint contracture. However, the underlying mechanism of joint capsule fibrosis is still controversial. The present study aims to establish an animal model of knee extending joint contracture in rats, and to investigate the role of hypoxia-mediated pyroptosis in the progression of joint contracture using this animal model. 36 male SD rats were selected, 6 of which were not immobilized and were used as control group, while 30 rats were divided into I-1 group (immobilized for 1 week following 7 weeks of free movement), I-2 group (immobilized for 2 weeks following 6 weeks of free movement), I-4 group (immobilized for 4 weeks following 4 weeks of free movement), I-6 group (immobilized for 6 weeks following 2 weeks of free movement) and I-8 group (immobilized for 8 weeks) according to different immobilizing time. The progression of joint contracture was assessed by the measurement of knee joint range of motion, collagen deposition in joint capsule was examined with Masson staining, protein expression levels of HIF-1α, NLRP3, Caspase-1, GSDMD-N, TGF-β1, α-SMA and p-Smad3 in joint capsule were assessed using western blotting, and the morphological changes of fibroblasts were observed by transmission electron microscopy. The degree of total and arthrogenic contracture progressed from the first week and lasted until the first eight weeks after immobilization. The degree of total and arthrogenic contracture progressed rapidly in the first four weeks after immobilization and then progressed slowly. Masson staining indicated that collagen deposition in joint capsule gradually increased in the first 8 weeks following immobilization. Western blotting analysis showed that the protein levels of HIF-1α continued to increase during the first 8 weeks of immobilization, and the protein levels of pyroptosis-related proteins NLRP3, Caspase-1, GSDMD-N continued to increase in the first 4 weeks after immobilization and then decreased. The protein levels of fibrosis-related proteins TGF-β1, p-Smad3 and α-SMA continued to increase in the first 8 weeks after immobilization. Transmission electron microscopy showed that 4 weeks of immobilization induced cell membrane rupture and cell contents overflow, which further indicated the activation of pyroptosis. Knee extending joint contracture animal model can be established by external immobilization orthosis in rats, and the activation of hypoxia-mediated pyroptosis may play a stimulating role in the process of joint capsule fibrosis and joint contracture.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Rats
Male
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Hypoxia metabolism
Hypoxia physiopathology
Disease Models, Animal
Transforming Growth Factor beta1 metabolism
Joint Capsule metabolism
Joint Capsule pathology
Joint Capsule physiopathology
Range of Motion, Articular
Smad3 Protein metabolism
Contracture metabolism
Contracture physiopathology
Contracture pathology
Pyroptosis physiology
Knee Joint pathology
Knee Joint metabolism
Knee Joint physiopathology
Rats, Sprague-Dawley
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2047-783X
- Volume :
- 29
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- European journal of medical research
- Publication Type :
- Academic Journal
- Accession number :
- 38802976
- Full Text :
- https://doi.org/10.1186/s40001-024-01890-9