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

F. Veronesi, G. Giavaresi, Melania Maglio, A. Scotto d'Abusco, L. Politi, R. Scandurra, Eleonora Olivotto, Brunella Grigolo, Rosa Maria Borzi', M. Fini

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)589-599
Number of pages11
JournalOsteoarthritis and Cartilage
DOIs
Publication statusAccepted/In press - May 27 2016

Fingerprint

Glucosamine
Tibial Meniscus
Knee Joint
Phenylalanine
Osteoarthritis
Inflammation
Derivatives
Cartilage
Surgery
Microhardness
Phosphotransferases
Intra-Articular Injections
Histology
Articular Cartilage
Extracellular Matrix
Bone
Animals
Enzymes
Joints
Immunohistochemistry

Keywords

  • IKKα pathway
  • Mouse model
  • NAPA
  • Osteoarthritis

ASJC Scopus subject areas

  • Rheumatology
  • Orthopedics and Sports Medicine
  • Biomedical Engineering

Cite this

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title = "Chondroprotective activity of N-acetyl phenylalanine glucosamine derivative on knee joint structure and inflammation in a murine model of osteoarthritis",
abstract = "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.",
keywords = "IKKα pathway, Mouse model, NAPA, Osteoarthritis",
author = "F. Veronesi and G. Giavaresi and Melania Maglio and {Scotto d'Abusco}, A. and L. Politi and R. Scandurra and Eleonora Olivotto and Brunella Grigolo and Borzi', {Rosa Maria} and M. Fini",
year = "2016",
month = "5",
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doi = "10.1016/j.joca.2016.10.021",
language = "English",
pages = "589--599",
journal = "Osteoarthritis and Cartilage",
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TY - JOUR

T1 - Chondroprotective activity of N-acetyl phenylalanine glucosamine derivative on knee joint structure and inflammation in a murine model of osteoarthritis

AU - Veronesi, F.

AU - Giavaresi, G.

AU - Maglio, Melania

AU - Scotto d'Abusco, A.

AU - Politi, L.

AU - Scandurra, R.

AU - Olivotto, Eleonora

AU - Grigolo, Brunella

AU - Borzi', Rosa Maria

AU - Fini, M.

PY - 2016/5/27

Y1 - 2016/5/27

N2 - 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.

AB - 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.

KW - IKKα pathway

KW - Mouse model

KW - NAPA

KW - Osteoarthritis

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EP - 599

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SN - 1063-4584

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