Abnormal loading of the knee due to injuries or obesity is thought to contribute to the development of osteoarthritis (OA). Small animal models have been used for studying OA progression mechanisms. However, numerical models to study cartilage responses under dynamic loading in preclinical animal models have not been developed. Here we present a musculoskeletal finite element model of a rat knee joint to evaluate cartilage biomechanical responses during a gait cycle. The rat knee joint geometries were obtained from a 3-D MRI dataset and the boundary conditions regarding loading in the joint were extracted from a musculoskeletal model of the rat hindlimb. The fibril-reinforced poroelastic (FRPE) properties of the rat cartilage were derived from data of mechanical indentation tests. Our numerical results showed the relevance of simulating anatomical and locomotion characteristics in the rat knee joint for estimating tissue responses such as contact pressures, stresses, strains, and fluid pressures. We found that the contact pressure and maximum principal strain were virtually constant in the medial compartment whereas they showed the highest values at the beginning of the gait cycle in the lateral compartment. Furthermore, we found that the maximum principal stress increased during the stance phase of gait, with the greatest values at midstance. We anticipate that our approach serves as a first step towards investigating the effects of gait abnormalities on the adaptation and degeneration of rat knee joint tissues and could be used to evaluate biomechanically-driven mechanisms of the progression of OA as a consequence of joint injury or obesity.
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http://dx.doi.org/10.1371/journal.pcbi.1009398 | DOI Listing |
Gene Ther
January 2025
School of Pharmacy, East China University of Science and Technology, Shanghai, China.
Osteoarthritis (OA), a prevalent joint disorder, can lead to disability, with no effective treatment available. Interleukin-1 (IL-1) plays a crucial role in the progression of OA, and its receptor antagonist (IL-1Ra), a natural IL-1 inhibitor, represents a promising therapeutic target by obstructing the IL-1 signaling pathway. This study delivered IL-1Ra via adeno-associated virus (AAV), a gene therapy vector enabling long-term protein expression, to treat knee osteoarthritis (KOA) in animal models.
View Article and Find Full Text PDFJB JS Open Access
January 2025
Gluck Equine Research Center, Department of Veterinary Science, Martin-Gatton College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky.
Background: Therapies for cartilage restoration are of great interest, but current options provide limited results. In salamanders, interzone (IZN) tissue can regenerate large joint lesions. The mammalian homolog to this tissue exists during fetal development and exhibits remarkable chondrogenesis in vitro.
View Article and Find Full Text PDFOsteoarthr Cartil Open
March 2025
Université de Lorraine, CNRS (French National Centre for Scientific Research), IMoPA (Molecular Engineering and Articular Physiopathology), F-54000, Nancy, France.
Objective: Osteoarthritis (OA) is the most common form of chronic joint disease, affecting mainly the elderly population. This disorder is caused by cartilage degeneration with complex changes in the chondrocyte phenotype. Inorganic pyrophosphate (PPi) was shown to counteract the detrimental effect of interleukin (IL)-1β challenging in an in vitro OA model based on rat articular chondrocytes.
View Article and Find Full Text PDFZhongguo Zhong Yao Za Zhi
December 2024
Hunan University of Chinese Medicine Changsha 410208, China Hunan Academy of Chinese Medicine Changsha 410013, China.
In order to elucidate the therapeutic effect and mechanism of action of Zhengqing Fengtongning Sustained-release Tablets on knee osteoarthritis, this study created a knee osteoarthritis model using 0.2 mL 40 g·L~(-1) papain and randomly divided the rats into the model group, high-dose and low-dose groups of Zhengqing Fengtongning Sustained-release Tablets, and celecoxib group. All groups were given the drug for four weeks, with the diameter of their knee joint being measured during this period.
View Article and Find Full Text PDFClin Rheumatol
January 2025
Department of Rheumatology and Immunology, Arthritis Research Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, 230000, China.
Objective: Nuclear transcription factor-κB (NF-κB) activation is a pivotal event in the pathogenesis of osteoarthritis (OA). OA patients frequently exhibit vitamin D (VD) deficiency, which is commonly associated with NF-κB activation. Our study aimed to investigate whether VD could protect against OA by modulating NF-κB pathway and to explore the underlying mechanisms.
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