title: An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis.
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 (NPs) 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.
authors: Environmental Health Research Institute, School of Food Science and Environmental Health, Dublin Institute of Technology, Dublin 1, Cathal Brugha St., Ireland.
authors: Sinéad M
authors: SM
authors: Ryan
authors: Jason
authors: J
authors: McMorrow
authors: Anita
authors: A
authors: Umerska
authors: Hetal B
authors: HB
authors: Patel
authors: Kristin N
authors: KN
authors: Kornerup
authors: Lidia
authors: L
authors: Tajber
authors: Evelyn P
authors: EP
authors: Murphy
authors: Mauro
authors: M
authors: Perretti
authors: Owen I
authors: OI
authors: Corrigan
authors: David J
authors: DJ
authors: Brayden
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002116:Calcitonin / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger; C028815:salmon calcitonin; D006820:Hyaluronic Acid; D002116:Calcitonin; D048271:Chitosan; D000242:Cyclic AMP; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse