Influence of mechanical conditioning and the C-type natriuretic peptide in the modulation of osteoarthritis (ARUK and AOF)

Principal investigator: Tina CHOWDHURY
Co-investigator(s): M. Ramachandran, P. Achan, D.M. Salter, A.J. Hobbs, and N. Peake

Comparison of Npr2 and Npr3 expression in normal and diseased cartilage from a single donor aged 60 yr.  CNP plays a critical role in the development and regulation of articular cartilage by promoting extracellular matrix production and chondrocyte proliferation. Our previous studies demonstrate that CNP acts to inhibit catabolic signals in response to IL-1β, and that these effects are synergistic with the protective stimuli induced by mechanical loading. The present study demonstrates that endogenous CNP / Npr2 / cGMP signalling route mediates anabolic events and prevents catabolic activities induced by IL-1. Stimulation with biomechanical signals and natriuretic peptide signals further augments the anabolic response resulting in a reduction of catabolic events mediated by a novel homeostatic pathway involving Npr2 / cGMP /PKGII route. Therapeutic application of CNP, or interventions targeted to natriuretic peptide receptors to mimic the actions of CNP should therefore be considered to speed up repair mechanisms and stabilise cartilage homeostasis in osteoarthritic conditions. In summary, the findings from this research will provide a new biophysical agent to prevent the pathophysiological mechanisms and treat OA in the young and old.

Mechanism showing the protective effects of CNPThis project is funded by the AO Foundation (S-09-83C) and Arthritis Research UK (19646) and supports Dr Nick Peake (PDRA). A short video describing the research can be viewed at: