An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis

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Title: An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis
Authors: Ryan, Sinéad M.
McMorrow, Jason P.
Umerska, Anita
Patel, Hetal B.
Kornerup, Kristin N.
Tajber, Lidia
Murphy, Evelyn
Perretti, Mauro
Corrigan, Owen I.
Brayden, David James
Permanent link: http://hdl.handle.net/10197/4364
Date: 28-Apr-2013
Abstract: Prolonged inappropriate inflammatory responses contribute to the pathogenesis of rheumatoid arthritis (RA) and to aspects of osteoarthritis (OA). The orphan nuclear receptor, NR4A2, is a key regulator and potential biomarker for inflammation and represents a potentially valuable therapeutic target. Both salmon calcitonin (sCT) and hyaluronic acid (HA) attenuated activated mRNA expression of NR4A1, NR4A2, NR4A3, and matrix metalloproteinases (MMPs) 1, 3 and 13 in three human cell lines: SW1353 chondrocytes, U937 and THP-1 monocytes. Ad-mixtures of sCT and HA further down-regulated expression of NR4A2 compared to either agent alone at specific concentrations, hence the rationale for their formulation in nanocomplexes (NP) using chitosan. The sCT released from NP stimulated cAMP production in human T47D breast cancer cells expressing sCT receptors. When NP were injected by the intra-articular (I.A.) route to the mouse knee during on-going inflammatory arthritis of the K/BxN serum transfer model, joint inflammation was reduced together with NR4A2 expression, and local bone architecture was preserved. These data highlight remarkable anti-inflammatory effects of sCT and HA at the level of reducing NR4A2 mRNA expression in vitro. Combining them in NP elicits anti-arthritic effects in vivo following I. A. delivery.
Type of material: Journal Article
Publisher: Elsevier
Copyright (published version): 2013 Elsevier B.V.
Keywords: Salmon calcitonin;Hyaluronic acid;NR4A orphan nuclear receptors;K/BxN serum;Inflammatory arthritis;Knee inflammation
DOI: 10.1016/j.jconrel.2013.01.027
Language: en
Status of Item: Peer reviewed
Appears in Collections:Veterinary Medicine Research Collection

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