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Target for possible osteoarthritis treatment found in RORβ protein

Posted: 18 October 2022 | | No comments yet

A new study has revealed that activating the RORβ protein could lead to a possible treatment and prevention for osteoarthritis.

osteoarthritis

In a study published in the journal PLOS One, Dr Patrick Griffin and Dr Mi Ra Chang from the University of Florida, US, describe a specific protein that manages activities within chondrocytes, a critical cell type that maintains healthy cartilage in joints.

Scientists at UF Scripps Biomedical Research revealed this is a possible new target to fight wear and tear in joints, where chondrocytes begin to fail. The team found that activating a specific protein in these cells called retinoic acid receptor-related orphan receptor beta (RORβ) could restore multiple factors needed for smooth joints to healthier levels, helping to control inflammation.

RORβ is a nuclear receptor that  when bound to DNA, activates the cell’s process of transcribing genes into proteins. Activating RORβ could therefore present a useful new strategy in preventing or delaying development of osteoarthritis.

Griffin has studied causes of bone diseases for many years. He zeroed in on RORβ for several reasons: while few studies have been focused on this receptor, some had shown correlation between the receptor’s activity and bone loss. Thus, he and Chang set out to better understand it, with Chang engineering cell lines to enable the studies.

“People need an osteoarthritis medication that addresses the root cause of cartilage damage and depletion as there currently are no disease-modifying drugs for what is the number one cause of disability in the US,” Griffin said. “While our work is in the early stages, our study suggests that the nuclear receptor RORβ could present a novel therapeutic target to protect cartilage damage and perhaps turn on cartilage regeneration.”

“To our surprise, the gene programme upregulated by increase in RORβ activity was supportive of the formation of chondrocytes, anti-inflammatory and protective against cartilage degradation,” Chang said.

“This study suggests RORβ could be an attractive therapeutic target. However, there is much more we need to unravel,” Griffin said. “Specifically, we want to understand more about the mechanism by which RORβ impacts chondrocytes and blunts the inflammatory signals that lead to cartilage destruction.”

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