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

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.