Protein Injection Shows Promise for Cartilage and Bone Regeneration in Osteoarthritis

Key Takeaways

Agrin, a protein tested in animals, helped regenerate cartilage and bone after joint injury.
It works by triggering local stem cells and blocking pathways that usually prevent cartilage growth.
The injection could be a simpler, less invasive alternative to surgery, but it hasn’t been tested in humans.
Questions remain about how well it will work in aging joints, long-term safety, and whether it will be affordable or widely accessible.

Agrin injections promoted cartilage and bone repair in animal models. Credit: Science Translational Medicine

Could a single protein help your joints heal themselves, without surgery?

That’s the question researchers at Queen Mary University of London are exploring in a breakthrough preclinical study that could shape the future of osteoarthritis treatment.

A team of bioengineers has developed an innovative approach to repairing joint injuries using agrin, a protein traditionally known for stabilizing neuromuscular connections. Their study, published in Science Translational Medicine, shows that agrin can regenerate cartilage and bone in injured joints, at least in animal models like mice and sheep. While human trials are still a step away, the results are raising cautious optimism among experts in regenerative medicine.

How Agrin Stimulates Joint Repair

In the study, researchers injected agrin mixed with a collagen gel into damaged knee joints. In both mice and sheep, the treatment helped restore cartilage and the underlying bone. These findings suggest that agrin activates a specific type of joint-resident stem cell and triggers a chain of biological processes that rebuild joint tissue.

What makes agrin especially promising is its dual action: it blocks a signaling pathway (WNT/β-catenin) that typically suppresses cartilage formation while also activating another pathway (CREB) that promotes chondrogenesis—the process by which stem cells become cartilage-producing cells. This combination enabled long-lasting regeneration in animal models, even in injuries that typically don’t heal on their own.

In the study, agrin was tested in both mice and sheep with surgically induced osteochondral defects—injuries that normally fail to heal completely. The protein was delivered via a type I collagen gel directly into the defect. In mice, cartilage and bone regeneration were assessed eight weeks post-treatment using Safranin O staining, histological scoring, and imaging. In sheep, joints were evaluated after six months, with improvements noted in both bone repair and functional behavior, such as increased physical activity. The researchers observed that agrin worked by recruiting GDF5-lineage stem cells to the injury site, activating CREB signaling, and suppressing canonical WNT signaling downstream of β-catenin, a critical step in promoting stable cartilage formation rather than scar tissue or bone.

Minimally Invasive and Potentially Affordable

Unlike many cartilage repair techniques that require surgery or stem cell harvesting, this agrin-based method involves a simple injection. According to lead author Professor Francesco Dell’Accio, this makes the treatment easier to administer, more scalable, and potentially lower in cost.

“The method does not require open surgery, making it easier to administer. Its lower cost also makes it accessible to more healthcare systems and easier for more healthcare professionals to use,” said Dell’Accio, Professor of Musculoskeletal Regenerative Medicine.

Limitations and the Road to Human Trials

Despite the promising results, the research is still in preclinical stages. The studies were conducted in mice and sheep, and human trials have not yet begun. Moreover, researchers delivered the protein shortly after surgically induced injuries in otherwise healthy joints. This raises questions about how effective the treatment would be in older adults with chronic joint degeneration or osteoarthritis-related inflammation. Older joints often have scar tissue, lower cell activity, and chronic inflammation — all of which can reduce healing potential.

The researchers acknowledge these limitations. The next phase will involve testing agrin in more complex scenarios, including joints affected by osteoarthritis—a disease that affects over 500 million people worldwide and remains without a cure.

“Because healing slows with age, we plan to first test agrin in younger individuals with sports injuries, then move toward trials in older patients,” said Dr. Suzanne Eldridge, co-lead author and Senior Lecturer at Queen Mary.

Why This Study Matters

Cartilage doesn’t heal easily, and current therapies mostly focus on managing symptoms, not restoring tissue. Agrin’s ability to regenerate joint surfaces without forming unwanted tissue like bone or scar could make it a game-changer, especially if results hold up in humans.

Still, readers should note that this is not yet a treatment option. Much of the work so far has been in the lab and in animal studies, which often don’t translate directly to people. Additional safety testing, dosage optimization, and long-term efficacy studies are all needed before agrin could be used in clinical practice.

Importantly, the study’s lead authors have filed a patent on agrin for cartilage regeneration—a fact that should be considered when evaluating the study’s conclusions.

FAQs About Agrin and Cartilage Repair

What is agrin and why are scientists excited about it?
It’s a protein your body already makes, mostly for nerve-muscle connections. Researchers found it also seems to “wake up” certain stem cells in joints, triggering cartilage and bone repair.

Has this been tested in people yet?
Not yet. The research was done in animals, specifically mice and sheep. Human testing is still ahead.

How was the study actually run?
They created joint damage in animals, then injected a mix of agrin and collagen gel into the injury. Over time, the damaged areas showed signs of healing that wouldn’t normally happen on their own.

So, it rebuilt cartilage?
In the study, yes. The repaired tissue looked like healthy cartilage under the microscope, and the bone underneath healed, too.

Would this work in older adults with arthritis?
That’s still a big unknown. The animals were young and healthy. Aging joints have more inflammation and wear, which could make things harder.

How does it work at the cellular level?
Agrin tells joint-resident stem cells to turn into cartilage-forming cells. It also shuts off signals that normally block cartilage growth.

Is this something that could replace surgery?
Potentially, yes — at least in certain cases. The idea is that it could be injected instead of needing an operation, especially for smaller defects.

Will it be affordable?
Hard to say. Agrin is tricky to produce, and the rights are already patented. That could push up the price, especially at launch.

Any safety concerns?
Agrin affects major cell pathways — including ones linked to growth and cancer — so researchers will need to watch for side effects, especially with long-term use.

Could people use this to “upgrade” their joints?
If it works well, there’s a chance it could be used outside of medical necessity — for athletic recovery, for example. That brings up questions about fairness and regulation.

What’s next?
More testing, ideally in older, arthritic joints, followed by human trials. Researchers will also need to figure out the right dose and how long the effects last.

The Bottom Line

If agrin lives up to its early promise, it could reshape how joint injuries are treated. But as with any breakthrough, the reality may be more complicated.

Aging joints aren’t easy to fix. The regenerative environment in older adults, often inflamed or structurally unstable, is very different from the clean, surgically created injuries used in animal trials. Whether agrin can overcome that challenge remains to be seen.

Cost is another factor. While the delivery method is simple, producing agrin at scale isn’t. It’s a large, complex protein, and with a patent already in place, pricing and access may be dictated by commercial interests, at least in the early years.

There are scientific unknowns, too. Agrin influences key developmental pathways, like WNT signaling, that are also involved in cancer and abnormal growth. Modulating these in humans could carry risks we don’t yet understand.

Then there’s the big picture: if we can truly rebuild joints, does this become a treatment — or a form of enhancement? A fix for age-related damage, or a tool for elite performance?

Agrin may be just one protein, but it opens the door to a future where we do more than manage disease — we might rebuild what time has worn down. Whether that future is safe, fair, or widely available is still an open question.

References

Eldridge, S. E., Barawi, A., Wang, H., Roelofs, A. J., Kaneva, M., Guan, Z., Lydon, H., Thomas, B. L., Thorup, A. S., Fernandez, B. F., Caxaria, S., Strachan, D., Ali, A., Shanmuganathan, K., Pitzalis, C., Whiteford, J. R., Henson, F., McCaskie, A. W., De Bari, C., & Dell’Accio, F. (2020). Agrin induces long-term osteochondral regeneration by supporting repair morphogenesis. Science Translational Medicine, 12(559), eaax9086. https://doi.org/10.1126/scitranslmed.aax9086