Enzyme discovery could lead to new osteoarthritis treatments

Enzymes appear to play a key role in joint destruction, a finding that could lead to new treatments, says research in Arthritis & Rheumatology.

Chondrocytes usually balance the production and destruction of molecules that make up cartilage. LRP1 removes proteins that could damage the cartilage. But in osteoarthritis, LRP1 levels are inhibited by other molecules (LRP1 sheddases) which upsets the balance.

Until now it has not been known which molecules act as LRP1 sheddases in human cartilage. The new work has identified the membrane-bound metalloproteinase enzymes ADAM17 and MMP-14 as the culprits.

The team involved found that blocking the activity of these enzymes restored the capabilities of the chondrocytes, leading to reduced joint cartilage degradation. Making a new drug to perform this function could therefore maintain healthy cartilage, repair damaged tissue and slow the accelerated breakdown of cartilage associated with osteoarthritis.

Devi Sagar from Arthritis Research UK comments:

“This is an exciting discovery in the quest for better treatment of osteoarthritis, a condition that can make everyday life harder for at least eight million people in the UK alone.

“Understanding what causes cartilage to break down in osteoarthritis is essential in order to identify treatments that could more effectively treat the condition and help people to push back the limits of their arthritis.”

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