Effects of losartan and atorvastatin on the development of early posttraumatic joint stiffness in a rat model.
antifibrotic drugs
bone sialoprotein
knee joint contracture
myofibroblast
posttraumatic joint stiffness
rat model
Journal
Drug design, development and therapy
ISSN: 1177-8881
Titre abrégé: Drug Des Devel Ther
Pays: New Zealand
ID NLM: 101475745
Informations de publication
Date de publication:
2019
2019
Historique:
received:
21
02
2019
accepted:
27
06
2019
entrez:
24
8
2019
pubmed:
24
8
2019
medline:
9
4
2020
Statut:
epublish
Résumé
After a trauma, exuberant tissue healing with fibrosis of the joint capsule can lead to posttraumatic joint stiffness (PTJS). Losartan and atorvastatin have both shown their antifibrotic effects in different organ systems. The purpose of this study was the evaluation of the influence of losartan and atorvastatin on the early development of joint contracture. In addition to joint angles, the change in myofibroblast numbers and the distribution of bone sialoprotein (BSP) were assessed. In this randomized and blinded experimental study with 24 rats, losartan and atorvastatin were compared to a placebo. After an initial joint injury, rat knees were immobilized with a Kirschner wire. Rats received either losartan, atorvastatin or a placebo orally daily. After 14 days, joint angle measurements and histological assessments were performed. Losartan increased the length of the inferior joint capsule. Joint angle and other capsule length measurements did not reveal significant differences between both drugs and the placebo. At cellular level both losartan and atorvastatin reduced the total number of myofibroblasts (losartan: 191±77, atorvastatin: 98±58, placebo: 319±113 per counting field, Both atorvastatin and losartan reduced the number of myofibroblasts in the posterior knee joint capsule of rat knees 2 weeks after trauma and losartan increased the length of the inferior joint capsule. However, these changes at the cellular level did not translate an increase in range of motion of the rats´ knee joints during early contracture development.
Sections du résumé
BACKGROUND
BACKGROUND
After a trauma, exuberant tissue healing with fibrosis of the joint capsule can lead to posttraumatic joint stiffness (PTJS). Losartan and atorvastatin have both shown their antifibrotic effects in different organ systems.
OBJECTIVE
OBJECTIVE
The purpose of this study was the evaluation of the influence of losartan and atorvastatin on the early development of joint contracture. In addition to joint angles, the change in myofibroblast numbers and the distribution of bone sialoprotein (BSP) were assessed.
STUDY DESIGN AND METHODS
METHODS
In this randomized and blinded experimental study with 24 rats, losartan and atorvastatin were compared to a placebo. After an initial joint injury, rat knees were immobilized with a Kirschner wire. Rats received either losartan, atorvastatin or a placebo orally daily. After 14 days, joint angle measurements and histological assessments were performed.
RESULTS
RESULTS
Losartan increased the length of the inferior joint capsule. Joint angle and other capsule length measurements did not reveal significant differences between both drugs and the placebo. At cellular level both losartan and atorvastatin reduced the total number of myofibroblasts (losartan: 191±77, atorvastatin: 98±58, placebo: 319±113 per counting field,
CONCLUSION
CONCLUSIONS
Both atorvastatin and losartan reduced the number of myofibroblasts in the posterior knee joint capsule of rat knees 2 weeks after trauma and losartan increased the length of the inferior joint capsule. However, these changes at the cellular level did not translate an increase in range of motion of the rats´ knee joints during early contracture development.
Identifiants
pubmed: 31440039
doi: 10.2147/DDDT.S204135
pii: 204135
pmc: PMC6679684
doi:
Substances chimiques
Atorvastatin
A0JWA85V8F
Losartan
JMS50MPO89
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2603-2618Déclaration de conflit d'intérêts
Dr Andreas Baranowski reports grants from the Johannes Gutenberg-University Mainz and the German Society of Shoulder and Elbow Surgery (DVSE), during the conduct of the study. Dr Anja Klein reports grants from the German Society of Shoulder and Elbow Surgery (DVSE) and Inneruniversitäre Forschungsförderung Stufe I, during the conduct of the study. The authors report no other conflicts of interest in this work.
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