Cartilage furthers its own destruction in arthritis

Cartilage actively participates in the destruction and remodelling of joints that occurs in rheumatoid arthritis by producing suppressors of cytokine signalling (SOCS) chemicals that induce inflammation.

Researchers at the Walter and Eliza Hall Institute in Melbourne made the discovery while investigating the role of the protein SOCS3 in controlling inflammation during rheumatoid arthritis.

Rheumatoid arthritis causes chronic pain and inflammation in joints such as those in the hands and feet, as well as knees and hips. Over time, the disease can destroy the cartilage that lubricates and cushions the joints, while bones can be remodelled, leading to disfigurement, pain and reduced mobility.

Dr Tommy Liu said the breakdown of cartilage was previously thought to be the consequence of an overactive immune system rather than playing an active role in rheumatoid arthritis.

“Autoimmune diseases such as rheumatoid arthritis are the result of the immune system wrongly attacking normal, healthy tissue,” Liu said. “Our study has shown for the first time that cartilage participates in the production of inflammation-signalling chemicals and contributes to its own destruction.”

The study investigated how SOCS molecules regulate inflammation in rheumatoid arthritis. The researchers created a mouse model that lacked SOCS3 molecules in cartilage and found that tissue degradation increased.

“Without SOCS3, cartilage cells produced enzymes that drove tissue degradation and increased inflammation by releasing signalling molecules that triggered an increased autoimmune response,” Liu said. “We also found that cartilage could produce a protein called RANKL that triggers bone remodelling.

“These results show that cartilage is not an innocent bystander that gets damaged as a result of rheumatoid arthritis, but instead plays an active role in disease progression.”

There is no cure for rheumatoid arthritis, and few treatments are effective in slowing the onset of the disease. “Targeting the action of these inflammatory chemical messages could boost the efficacy of current treatments,” Liu said.

The study was published in the journal Arthritis and Rheumatology.