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New research shows that disrupting primary cilia in juvenile, adolescent and early adulthood in cartilage stops it maturing correctly, making it more prone to thinning and the potential for osteoarthritis (OA) in later life.

Illustration of cilia

Published in the journal Arthritis and Rheumatologythe study looked at the role of proteins associated with primary cilia in post-natal cartilage development, and the health of adult cartilage.  

Angus Wann, KTRR/Versus Arthritis Research Fellow and senior author said: Wobserved a thinning of the cartilage that was due to the removal of a ‘brake’ which is dampening a developmental biological program to ensure the formation of cartilage that is fit for purpose for life-long mechanical loading.”  

The ‘brake’ was shown to be theprotein IFT88, found in the cilia. The developmental pathway (Hh signalling) being kept in check by IFT88 is also abnormally activated in human OA and the group found exercise restored normal levels of Hh signalling when cilia are disruptedAbnormal responses to mechanical forces underlie many diseases of cartilage and bone. Our results suggest that cilia may help integrate biological signalling with mechanical inputs to maintain healthy adult cartilage,” said Angus. “Ultimately, we have shown primary cilia are still very important in the adult knee, safeguarding cartilage integrity.   

The team is now working to understand how cells in cartilage use cilia to make the “right” decisions supporting healthy biological signalling in the face of what might otherwise be disease-causing challenges to the tissue.  

Understanding how cells use cilia to help them respond appropriately to signals such as mechanical forces, will help the understanding why many cartilage and bone disorders develop and identify new ways to protect against this.   

This research was primarily funded by the Kennedy Trust through a fellowship to Angus and studentship to Clarissa Coveney, and was also heavily supported by Versus Arthritis through the Centre for OA pathogenesis. 

 

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