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 language | English |
|---|---|
| Pages (from-to) | 589-599 |
| Number of pages | 11 |
| Journal | Osteoarthritis and Cartilage |
| DOIs | |
| Publication status | Accepted/In press - May 27 2016 |
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Keywords
- IKKα pathway
- Mouse model
- NAPA
- Osteoarthritis
ASJC Scopus subject areas
- Rheumatology
- Orthopedics and Sports Medicine
- Biomedical Engineering
Cite this
Chondroprotective activity of N-acetyl phenylalanine glucosamine derivative on knee joint structure and inflammation in a murine model of osteoarthritis. / Veronesi, F.; Giavaresi, G.; Maglio, Melania; Scotto d'Abusco, A.; Politi, L.; Scandurra, R.; Olivotto, Eleonora; Grigolo, Brunella; Borzi', Rosa Maria; Fini, M.
In: Osteoarthritis and Cartilage, 27.05.2016, p. 589-599.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=85006930203&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006930203&partnerID=8YFLogxK
U2 - 10.1016/j.joca.2016.10.021
DO - 10.1016/j.joca.2016.10.021
M3 - Article
SP - 589
EP - 599
JO - Osteoarthritis and Cartilage
JF - Osteoarthritis and Cartilage
SN - 1063-4584
ER -