‘Dancing molecules’ could help repair cartilage damaged by…

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Osteoarthritis is a common and chronic condition that can involve cartilage damage.
Researchers are interested in finding ways to address cartilage damage.
In a recent study, researchers designed ‘dancing molecules’ that could be key in boosting cartilage repair.
Osteoarthritis is a chronic condition that affects joints and can lead to cartilage degradation.
Osteoarthritis
Current treatment options for osteoarthritis often focus on symptom management, but researchers are also interested in what would need to happen for cartilage repair to take place.
One area of interest is the possibility of using the protein transforming growth factor (TGF)-β1 to assist with cartilage repair and in what circumstances this protein can be most effective.
A study recently published in the Journal of the American Chemical Society examined applying a mimic of the TGF-β1 peptide with a circular structure to induce cartilage repair.
Journal of the American Chemical Society
Researchers found that a version of the TGF-β1 peptide mimic that was designed to have freer movement led to the best results.
‘Dancing molecules’ most effective in cartilage repair
Cartilage is a special type of tissue in the body that helps to cushion joints. Changes in this cartilage are part of what can happen when someone has osteoarthritis.
Cartilage
Chondrocytes are the cells that make up cartilage and help maintain the extracellular matrix. In osteoarthritis, joint cartilage can become damaged, leading to movement struggles and pain in the affected joints.
Chondrocytes
Study author Samuel I. Stupp, PhD, professor in the Department of Chemistry at the Weinberg College of Arts and Sciences at Northwestern University, IL, explained to Medical News Today:
Samuel I. Stupp, PhD
“Cartilage tissue, which is a critical component of all our major joints in the body, is a tissue that contrary to other tissues […] does not have the capacity to regenerate in adults […] [This study] aims at finding ways of developing materials that regenerate cartilage.”
Researchers looked at creating a specific molecular substance that contained peptide amphiphiles (PA), which are a type of self-assembling molecules, and a transforming growth factor TGF-β1 mimetic epitope.
Mimetic epitopes are synthetic molecules that mimic the structures and functions of corresponding molecules on the surface of specific proteins.
Mimetic epitopes
The researchers confirmed that a circular growth factor mimetic peptide was the most effective structure to use compared to a linear structure.
Researchers examined the effects on human joint chondrocytes and confirmed that the circular epitope helped activate TGF-β1 signaling in the cartilage cells.
They also found that one circular epitope assembly that moved more freely better promoted the production of factors involved in cartilage regeneration. These results indicate that increasing movement in these epitope assemblies helps to boost the effective response in chondrocytes, compared to assemblies with less movement.
The researchers essentially turned their assemblies into what they dub “dancing molecules,” which they found to be more effective at stimulating cartilage repair.
“We changed the structure of the molecules to activate the motion of molecules. We had discovered back in 2021 that the motion of molecules is very important in making them very effective at signaling cells,” Stupp explained.
The current study “was the second discovery that this motion of the molecules is important in completely different biology,” he told us. “We verified that the supramolecular motion is also important in cartilage. We tested it in human cartilage cells [and] found that the motion of the molecules made them [cartilage cells] produce larger amounts of the components of cartilage tissue.”
Overall, the results show promise in a new way to elicit cartilage repair, which could be very helpful for people with osteoarthritis.
Study limitations and continued research
This research does have limitations. The main limitation is that while researchers used human tissue, the study did not test the results in people. Thus, it is unclear how well the findings will translate to clinical practice, where other factors are involved.
Future research could replicate this study’s findings, increase precision, and explore even more of the underlying mechanisms.
Another study recently conducted by Stupp and his colleagues tested the use of a similar bioactive material in sheep. Stupp noted that they will need to test which bioactive material is the most effective before starting to seek approval for clinical trials.
study
“Once we have made our choice, then we have to do research in the lab to learn how to scale it up to larger quantities and to develop a manufacturing method so it can be commercialized. Then, the next step is to approach the FDA [Food and Drug Administration] to grant us approval to conduct the first clinical trial in patients,” Stupp told us.
Bert Mandelbaum, MD, sports medicine specialist and orthopedic surgeon at Kerlan-Jobe Institute and Co-Director of the Regenerative Orthobiologic Center at Cedars-Sinai Medical Center in Los Angeles, not involved in the current study, commented that:
Bert Mandelbaum, MD
“[Millions of people] worldwide are negatively impacted by cartilage degeneration. This is a very interesting study revealing some potentially new and exciting mechanisms. Systematically there needs to be more follow up, translating this to human considerations. There is potential, but it requires a systematic path of different proof of concept studies and then lastly, physically translating it to human beings in order to prove its efficacy.”
Renewed hope for people with osteoarthritis
Osteoarthritis is challenging to manage and impacts many people in the United States and worldwide. In the U.S., 21.2% of adults have been diagnosed with some type of arthritis. Worldwide, over 500 million people had osteoarthritis in 2019. People with osteoarthritis can be at an increased risk for falls and may struggle with their health-related quality of life.
21.2%
500 million
health-related quality of life
Studies like this one emphasize that research is moving forward to address the concerns of osteoarthritis and other conditions that involve cartilage damage. This research could improve treatment options and lead to better clinical outcomes and quality of life for people with osteoarthritis.
Jaya Sonkar, MD, MPH, founder and president of JSR Health Rheumatology, who was not involved in this research, noted that “[osteoarthritis] can significantly affect […] quality of life.”
Jaya Sonkar, MD, MPH
“Currently, treatment options mainly include conservative measures, pain relief, and physical therapy. Given its high prevalence and the considerable loss of Quality-Adjusted Life Years (QALY) it causes, advancing research into new treatment modalities is crucial,” she explained.
“Transforming growth factor-β1 (TGF-β1) plays a key role in the development of osteoarthritis. Recent research highlights promising aspects of TGF-β1 that could be pivotal in developing effective treatments. Although more research is needed and progress may be gradual, these insights offer hope for creating innovative treatments that could potentially transform the management of osteoarthritis and redefine old age,” said Sonkar.