Chondroprotective activity of N-acetyl phenylalanine glucosamine derivative on knee joint structure and inflammation in a murine model of osteoarthritis
Autor: | Melania Maglio, Gianluca Giavaresi, Roberto Scandurra, Brunella Grigolo, Rosa Maria Borzì, Laura Politi, Francesca Veronesi, A. Scotto d'Abusco, Eleonora Olivotto, Milena Fini |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Cartilage Articular Male Pathology medicine.medical_specialty Knee Joint mouse model Phenylalanine Biomedical Engineering Inflammation IκB kinase Osteoarthritis Pharmacology Menisci Tibial Proinflammatory cytokine Injections Intra-Articular Extracellular matrix 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Rheumatology IKKα pathway napa osteoarthritis Matrix Metalloproteinase 10 Glucosamine Matrix Metalloproteinase 13 medicine Animals Orthopedics and Sports Medicine Kinase activity 030203 arthritis & rheumatology NAPA Chemistry Organ Size Osteoarthritis Knee medicine.disease I-kappa B Kinase Disease Models Animal 030104 developmental biology ADAMTS5 Protein medicine.symptom |
Zdroj: | Osteoarthritis and cartilage. 25(4) |
ISSN: | 1522-9653 |
Popis: | Summary Objective Osteoarthritis (OA), the most common chronic degenerative joint disease, is characterized by joint structure changes and inflammation, both mediated by the IκB kinase (IKK) signalosome complex. The ability of N-acetyl phenylalanine derivative (NAPA) to increase cartilage matrix components and to reduce inflammatory cytokines, inhibiting IKKα kinase activity, has been observed in vitro . The present study aims to further clarify the effect of NAPA in counteracting OA progression, in an in vivo mouse model after destabilization of the medial meniscus (DMM). Design 26 mice were divided into three groups: (1) DMM surgery without treatment; (2) DMM surgery treated after 2 weeks with one intra-articular injection of NAPA (2.5 mM) and (3) no DMM surgery. At the end of experimental times, both knee joints of the animals were analyzed through histology, histomorphometry, immunohistochemistry and microhardness of subchondral bone (SB) tests. Results The injection of NAPA significantly improved cartilage thickness (CT) and reduced Chambers and Mankin modified scores and fibrillation index (FI), with weaker MMP13, ADAMTS5, MMP10 and IKKα staining. The microhardness measurements did not shown statistically significant differences between the different groups. Conclusions NAPA markedly improved the physical structure of articular cartilage while reducing catabolic enzymes, extracellular matrix (ECM) remodeling and IKKα expression, showing to be able to exert a chondroprotective activity in vivo . |
Databáze: | OpenAIRE |
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