The nuclear receptor RORβ is expected to be a new target for the prevention and treatment of osteoarthritis

Wear and tear on joints can lead to inflammation, cartilage destruction, and the development of
osteoarthritis.
Scientists at the Scripps Institute of Biomedical Research have discovered a possible new target to combat this painful chain reaction
.

Biochemist Dr.
Patrick Griffin and his colleague Dr.
Mi Ra Chang have discovered that RORβ is an important transcription factor involved in the regulation
of genetic programs that prevent joint cartilage damage.
The findings were published Oct.
13 in
the journal PLOS One.

As people age and their joints are stressed, their chondrocytes begin to decline
.
The research team found that activating a specific protein in these cells called RORβ can restore multiple factors needed for healthy joints, helping to control inflammation
.
Dr.
Griffin believes that activating RORβ is expected to be a new strategy
to prevent or delay the progression of osteoarthritis.

"People need an osteoarthritis drug to address the root causes of cartilage damage and depletion because there is currently no drug that can alleviate the disease, and cartilage damage is the number one cause of disability in the United States," Dr.
Griffin said
.
"Although our work is still in its early stages, our study suggests that the nuclear receptor RORβ may serve as a new therapeutic target to prevent cartilage damage and hopefully initiate cartilage regeneration
.
"

RORβ (retinoic acid receptor-associated orphan receptor β) is a member
of the nuclear receptor superfamily.
In our cells, genes are usually switched
between active and inactive periods.
When a nuclear receptor binds to DNA, it activates the process
in the cell that transcribes genes into proteins.
RORβ is involved in the development of the retina during fetal development, and it can also influence circadian rhythms by controlling clock genes, but its role in keeping cartilage healthy is unclear
.

Dr.
Griffin has been studying the causes of
bone diseases for years.
He recently focused on RORβ
.
While few studies have focused on this receptor, some studies have shown an association
between RORβ activity and bone loss.
So he and Chang set out to understand it
.
Chang engineered the cell line to support this research
.

"We were surprised that the upregulated gene program by increasing RORβ activity supported chondrocyte formation, anti-inflammatory effects, and prevented cartilage degradation," said
Dr.
Chang.

Dr.
Griffin said the research team has initiated more research
due to the huge demand for osteoarthritis solutions.
In the United States, an estimated 32 million people suffer from this painful disease
.

"This study suggests that RORβ may be an attractive therapeutic target
.
However, there are many mysteries that we need to solve," Griffin said
.
"Specifically, we wanted to gain insight into the mechanisms by
which RORβ affects chondrocytes and attenuates inflammatory signaling.
"

Original text search

Chang MR, Griffin PR (2022) RORβ modulates a gene program that is protective against articular cartilage damage.
PLoS ONE 17(10): e0268663.
https://doi.
org/10.
1371/journal.
pone.
0268663