New study identifies targets for blocking cartilage breakdown in osteoarthritis (published on 28 March 2017)

Scientists have made a potentially important discovery about the way that cartilage damage occurs in people with osteoarthritis, potentially opening the door for new treatments to be developed.
Funded by Versus Arthritis and led by Dr Kazuhiro Yamamoto at Oxford University's Kennedy Institute of Rheumatology, the study identified enzymes that play a key role in joint destruction, which could be targeted by future therapies. 

How these molecules contribute to osteoarthritis

Published in the medical journal Arthritis & Rheumatology, the research offers an important insight into how cartilage cells called chondrocytes are interrupted in their process of maintaining normal healthy cartilage due to the removal of a protein called LRP1.

Normally, chondrocytes balance the production and destruction of molecules making up cartilage, with LRP1 acting to remove proteins that could potentially cause excess damage to the cartilage. In osteoarthritis, however, LRP1 levels are inhibited by other molecules called LRP1 sheddases, upsetting this delicate balance.

Previously, it was not known which molecules act as LRP1 sheddases in human cartilage, but this new study identified the membrane-bound metalloproteinase enzymes ADAM17 and MMP-14 as the culprits.

The potential benefits for patients

Of particular importance was the fact that this research determined that blocking the activity of these enzymes restored the capabilities of the chondrocytes, leading to reduced degradation of the joint cartilage.
It suggests that creating a new drug to perform this function could deliver numerous benefits, including maintaining healthy cartilage, repairing damaged tissue and slowing the accelerated breakdown of cartilage associated with osteoarthritis.
The researchers concluded: "The shedding of LRP1 is a key link to osteoarthritis progression. Local inhibition of LRP1 sheddase activities of ADAM17 and MMP-14 is a unique way to reverse matrix degradation in osteoarthritis cartilage and could be effective as a therapeutic approach."

Our view

Devi Sagar, research liaison and communications manager, said: "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."

Published on 28 March 2017.

New fibroblast study offers insights in rheumatoid arthritis treatment (published on 25 November 2016)

British scientists have uncovered new insights into the key role of different types of fibroblast cells in the development of rheumatoid arthritis.The Versus Arthritis -funded study from the University of Birmingham has shed new light on the biological processes underpinning the disease, potentially opening the door for improved treatments to be developed.

How synovial fibroblasts drive the development of rheumatoid arthritis

Fibroblasts are a type of cell involved in the production of collagen and the structural materials that connect other cells in the body. This study focused on synovial fibroblasts, which make up part of the connective tissue around human joints.

It is known that in rheumatoid arthritis, these cells cause damage by invading and attacking the cartilage and bone around the joint; however, this research offered evidence that there may be two distinct types of synovial fibroblast, which was not previously known.

These two types were categorised by specific cell surface markers, PDPN and CD248, and it was shown that the part closest to the cartilage tended to contain the invasive PDPN-type fibroblasts that cause cartilage damage, while the part that was further away from the cartilage contained the non-invasive CD248 type.

Implications for new treatment strategies

This research could prove important in laying the foundation for new therapeutic strategies. Currently, the treatment of rheumatoid arthritis involves giving patients a combination of immunosuppressive drugs, which is known to carry the risk of a serious impact on their quality of life.

As such, this study's suggestion that targeting fibroblast cell processes could result in more effective and manageable treatments will be good news for patients.

Study leader Dr Adam Croft from the University of Birmingham said: "This study not only shows the existence of distinct subsets of synovial fibroblasts, but also suggests that these cells are able to self-organise into lining and sublining layers in the presence of cartilage.

"Combined with the difference in migration rates between the two types of cell, these results are extremely promising in terms of finding new therapeutic targets for treatment of rheumatoid arthritis."

Our view

Dr Natalie Carter, head of research liaison at Versus Arthritis, said: "Rheumatoid arthritis is an incredibly painful condition that affects around 290,000 people in the UK. This study is significant as it advances our knowledge of what actually occurs within the joint of someone who lives with the condition, and could lead to new, more targeted treatments.

Over the years, we have funded significant breakthroughs for rheumatoid arthritis such as anti-TNFs, which changed the treatment landscape. However, what works for one person may not work for another, and so there is an urgency for more effective treatments that will remove the need for a trial-and-error approach to treatment.

Published on 25 November 2016