Chondroprotective activity of N-acetyl phenylalanine glucosamine derivative on knee joint structure and inflammation in a murine model of osteoarthritis.
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).



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.



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.



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.
Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy. Electronic address: francesca.veronesi@ior.it.
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Veronesi
Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy. Electronic address: gianluca.giavaresi@ior.it.
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Giavaresi
Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Orthopedic Institute, Bologna, Italy. Electronic address: melania.maglio@ior.it.
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Maglio
Department of Biochemical Sciences, Sapienza University of Roma, Roma, Italy. Electronic address: anna.scottodabusco@uniroma1.it.
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Scotto d'Abusco
Department of Biochemical Sciences, Sapienza University of Roma, Roma, Italy. Electronic address: laura.politi@uniroma1.it.
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Politi
Department of Biochemical Sciences, Sapienza University of Roma, Roma, Italy. Electronic address: roberto.scandurra@uniroma1.it.
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Scandurra
Laboratory RAMSES-Research, Innovation & Technology Department, Rizzoli Orthopedic Research Institute, Bologna, Italy. Electronic address: Eleonora.olivotto@ior.it.
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Olivotto
Laboratory of Immunorheumatology and Tissue Regeneration/RAMSES, Rizzoli Orthopedic Institute, Bologna, Italy. Electronic address: brunella.grigolo@ior.it.
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Grigolo
Laboratory of Immunorheumatology and Tissue Regeneration/RAMSES, Rizzoli Orthopedic Institute, Bologna, Italy. Electronic address: rosamaria.borzi@ior.it.
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Borzì
Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy; Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Orthopedic Institute, Bologna, Italy. Electronic address: milena.fini@ior.it.
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Fini
D000071116:ADAMTS5 Protein / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005944:Glucosamine / Q000494:pharmacology*; D051550:I-kappa B Kinase / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000187:drug effects / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000187:drug effects / Q000378:metabolism; D008592:Menisci, Tibial / Q000601:surgery; D051379:Mice; D009929:Organ Size; D020370:Osteoarthritis, Knee / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology
D010649:Phenylalanine; D051550:I-kappa B Kinase; D000071116:ADAMTS5 Protein; C498489:Adamts5 protein, mouse; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D053506:Matrix Metalloproteinase 10; D005944:Glucosamine; C044228:N-acetylphenylalanine
IKKα pathway; Mouse model; NAPA; Osteoarthritis