Scientists are discovering a new treatment target for osteoarthritis-like knee cartilage shrinkage

There is currently no cure for osteoarthritis, but a group of scientists believe they have found a way in which a simple knee injection could stop the effects of the disease. These researchers showed that they were able to target a specific protein pathway in mice, put in excess and stop cartilage shrinkage over time. Building on that finding, they were able to show that treating mice with surgical-induced cartilage degeneration through the same pathway through nanomedicine arterial state could significantly reduce cartilage degeneration and knee pain. These results were published in Science Translational Medicine.

Our laboratory is one of the few in the world that studies signs of epidermal growth factor receptor (EGFR) in cartilage and, from the outset, we have found EGFR deficiency or inactivity. accelerates the progression of osteoarthritis in mice. Therefore, we suggested that its activation could be used to treat osteoarthritis, and in this study, we have shown for the first time that hyperactivity within the knee hinders progression. osteoarthritis. “

Ling Qin, PhD, Associate Professor of Orthopedic Surgery, Perelman School of Medicine, University of Pennsylvania

Qin explained that tests from the other laboratories working with EGFR have drawn “controversial and controversial” results. But Qin’s laboratory has consistently found the links between osteoarthritis and EGFR deficiencies, which formed the basis of the hypothesis.

The researchers compared normal mice with those with molecules that bound to EGFR, called a ligand, which was overstretched in chondrocytes, the building blocks of cartilage. This overexpression leads to overexpression of EGFR signals in knee cartilage. When examined, it was found that the mice with overexpressed HBEGF (the EGFR ligand) on cartilage expanded consistently, meaning that it did not wear off like the mice with normal EGFR activity. Moreover, when these mice became adults, their cartilage withstood degeneration and other symptoms of osteoarthritis, even though the meniscus of the knee was damaged.

To further prove that the proactive EGFR was the reason for the stability of the mice, the researchers found that gefitinib treatments, designed to inhibit EFGR action, provided protection against cartilage degeneration.

With all this experience gained, the researchers turned their attention to possible clinical treatment solutions. In a new series of experiments they created nanotherapeutics by binding a strong EGFR ligand, altering growth factor-alpha, on synthetic nanoparticles, to inject into mice that already had cartilage damage on their knees.

“Free EGFR ligands have a short half-life and cannot be contained within a composite capsule due to their small size,” explained Zhiliang Cheng, PhD, associate research professor in Penn Engineering and another of the corresponding authors on the paper. “Nanoparticles help protect them from shrinkage, contain them within the component, reduce toxicity where -target, and transport them deep inside dense cartilage to reach chondrocytes. “

When mice were introduced with these nanotherapeutics, the researchers found that they slowed down cartilage shrinkage and bone hardening, as well as reduced knee pain. No significant side effects were observed in the treated mice.

“While many of the technical aspects of this application still need to be worked out, the ability to stop or slow down the course of osteoarthritis with injection rather than surgery would significantly change how we feel. and work as we age and after an injury, ”said one of the study’s co-authors, Jaimo Ahn, MD, PhD, a former faculty member at Penn Medicine now head of orthopedic trauma and chair associated with orthopedic surgery at the University of Michigan.

The treatment seems to be a bit off-putting for human patients, but the nanoparticles already used are clinically tested and considered safe, which makes it easier to quickly translate into clinical use .

“There is a huge unmet medical need for disease-altering osteoarthritis drug,” Qin said. “In the future, we will design the best drug and test it in large animals before proceeding to clinical trials. We hope our research could lead to the development of a new drug that will improve health. and the well-being of more than 27 million osteoarthritis patients in the United States. “