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Could Gremlin 1 stem cells point to better osteoarthritis treatments? Image credit: IMAGINESTOCK/Getty Images.
  • About 7% of the world’s population has osteoarthritis.
  • There is currently no cure for osteoarthritis.
  • Researchers from the University of Adelaide have identified a specific type of stem cell they believe to be responsible for the progression of osteoarthritis, via a mouse model.
  • Scientists believe this finding may provide new avenues for treatment and even reversal of the disease.

More than 500 million people around the globe, or 7% of the world’s population, have osteoarthritis — a degenerative joint disease caused by tissues in the body’s joints wearing down over time.

Osteoarthritis is the most common type of arthritis.

There is currently no cure for this condition. Doctors use a variety of treatments to help relieve symptoms and keep joints mobile, including medications, physical therapy, joint replacement surgery and lifestyle modifications.

Now new research recently published in the journal Nature Communications says loss of a specific type of stem cell is responsible for the progression of osteoarthritis, via a mouse model.

Researchers from the University of Adelaide in Australia say this finding may provide new avenues for treatment and even reversal of the disease, and challenges the idea of osteoarthritis just being a “wear and tear” condition.

According to Dr. Jia Ng, a postdoctoral researcher in the School of Medicine at the University of Adelaide and the co-lead author of this study, there has been a huge unmet need for the treatment of osteoarthritis.

“Most treatments for osteoarthritis concentrate on treating the symptoms and improving the quality of life instead of targeting the disease, which leads ultimately to joint replacement surgery — this inevitable prospect also has a significant impact on [a] patient’s mental health,” she explained to Medical News Today.

Dr. Ng said it is important to show that osteoarthritis is not just the “wear and tear” condition many believe it to be:

“The original concept of osteoarthritis being a ‘wear and tear’ condition has an implication that the disease itself may not have pharmacological intervention to treat the disease and reverse the pathology. Wear and tear disease indicates that the progression of the disease is a matter of time and inevitable. By reimagining the disease, we provide an opportunity and more importantly, a pharmaceutical target for the medical community to discover new drugs to reverse and treat osteoarthritis.”

When looking at potential causes for the progression of osteoarthritis, Dr. Ng and her team decided to look at stem cells.

“As a stem cell biologist, [I’ve] worked with a variety of stem cell populations throughout my career,” she explained. “The initiation of many diseases’ progression [has] been shown to be the consequence of a compromised stem cell population, such as blood cancer and colorectal cancers.“

“The question for me was then, why not osteoarthritis? All mature cells develop from a particular discrete source of stem cell population — if we can fix the source of mature cells, we can treat and reverse the impairment of all mature cells and tissues,” she added.

Such cells, Dr. Ng explained, have “been shown to be the consequence of a compromised stem cell population, such as blood cancer and colorectal cancers.“

“The question for me was then, why not osteoarthritis? All mature cells develop from a particular discrete source of stem cell population — if we can fix the source of mature cells, we can treat and reverse the impairment of all mature cells and tissues.”

– Dr. Jia Ng

Scientists used a mouse model of osteoarthritis and identified a specific population of stem cells marked by the Gremlin 1 (Grem1) gene that they believe are responsible for the progression of osteoarthritis.

Grem1 gene is a family of bone morphogenic protein which has a role in regulating organogenesis, body patterning, and tissue differentiation,” Dr. Ng detailed. “Grem1 has also been shown to have roles in the intestine, bone marrow, pancreas, and brain. In the early stages of embryonic development, Grem1 is also involved in skeletogenesis — limb bud development. Hence, it was only natural to be curious about its role in skeletal diseases such as osteoarthritis.”

During the study, researchers found treatment with fibroblast growth factor 18 (FGF18) vitalized the rapid production of Grem1 cells in the joint cartilage of mice. This ultimately led to a significant recovery of cartilage thickness and reduced osteoarthritis.

“We believe that our discovery of these cells would lead to therapeutic advancement to treat the disease and reverse the pathology,” Dr. Ng said.

According to her, “[f]or the first time, we are providing pharmaceutical innovators a target for drug discovery. In fact, the proposed — not limited to — treatment FGF18 showed [an] indication of increased cartilage thickness post-treatment, a reverse of early pathology. This opens [the] door to other pharmaceutical options beyond FGF18.”

Dr. Ng said the biggest opportunity she and her team had through this research was to provide a target for osteoarthritis treatments that have been shown to work.

“There have been others based on the concept of stimulating the cartilage cells — chondrocytes — with varying success,” she explained. “Other stem cell therapies looked at stimulating the traditional mesenchymal stem cell population, which we have shed some light [on] in our paper to show that they may not actually be a suitable/effective target.”

“Phase 3 clinical trials in the U.S. [have] shown that using FGF18, a treatment that we have (shown) to target Grem1 cells, [has] extremely promising phase 2 results,” Dr. Ng added. “Similar drug discovery should aim for the same target to provide [a] better opportunity to reverse osteoarthritis pathology.”

MNT also spoke with Dr. Steve Yoon, physiatrist and director of The Regenerative Sports and Joint Clinic at Cedars-Sinai Kerlan-Jobe Institute in Los Angeles, not involved in the research, about this study.

“Anytime you see research being performed to try to help people with osteoarthritis, I think it’s, it’s always encouraging and promising,” he told us. “This type of research is essential — the next step is to continue understanding the mechanisms at play here and how it will affect humans.”

“Researchers are trying to find ways to try to help people because [osteoarthritis] is a worldwide problem,” Dr. Yoon continued.

“It’s important to let people know that there’s some hope and that people are trying to find ways to cure, if you will, or reverse the degenerative effect that you get on joints. And to just encourage people that it’s worthwhile to do your best to try to maintain what you have in hopes that maybe there could be something coming down the pipeline in the future.”

– Dr. Steve Yoon