A summer researching equine osteoarthritis and a potential treatment

Raised in Great Neck, New York, by parents who have always loved animals, rising second-year Sidney Wong began shadowing at a small-animal veterinary clinic her junior year of high school. Over time gaining the trust of staff to help with tasks such as bloodwork and customer service, Wong dreamed of someday opening her own clinic.

One of her first-year roommates at Penn told Wong, a pre-vet biology major, about the Penn Undergraduate Research Mentoring Program(PURM), a 10-week research opportunity through the Center for Undergraduate Research and Fellowshipsthat comes with a $5,000 award. Wong says it sounded like a great opportunity to dip her feet in veterinary research, and she has always been interested in work that can apply to humans as well as animals.

With a PURM grant, Wong has spent the summer in the lab of Kyla Ortved, the Jacques Jenny Endowed Term Chair of Orthopedic Surgery and associate professor of large animal surgery at the School of Veterinary Medicine, studying the pathophysiology of equine osteoarthritis and a potential therapy.

"Having an opportunity to step in as a total beginner into these amazing projects is a wonderful experience, and for me it's definitely been very rewarding," Wong says of PURM.

Ortved has been studying osteoarthritis, a joint disease in which cartilage progressively breaks down, since 2010. She says the many causes include the accumulation of small traumas over time or a single traumatic event, such as an ACL tear in humans or an intraarticular fracture in horses. The impacts of osteoarthritis can include chronic pain and decreased function at normal daily tasks for humans and chronic lameness for horses.

"It's not caused by a single factor. It's very complex and currently lacks any effective treatment that either reverses it or cures it or prevents it from occurring," Ortved says. About 33 million adults in the United States have osteoarthritis, according tothe Centers for Disease Control and Prevention.

Osteoarthritis also occurs frequently in horses, which have similar joint properties and cartilage thickness as humans, Ortved says. That makes them a good model for studying the disease and treatments that could benefit humans and horses alike.

One of Ortved's current studies investigates the epidermal growth factor receptor (EGFR) pathway, a signaling pathway in cartilage that promotes tissue growth. This builds off previous researchby her collaborators, Ling Qinof the Perelman School of Medicineand Zhiliang Chengof the School of Engineering and Applied Science, who found that activating this pathway decreases osteoarthritis in mice.

The Qin and Cheng labs developed nanoparticles bound with transforming growth factor alpha (TGF-α), a protein that increases signaling through the EGFR pathway, Ortved explains. She says the idea is to inject these nanoparticles into joints, thereby increasing the expression of good genes by cartilage cells and decreasing the expression of genes that inflame and degrade the cartilage.

Ortved says that, while EGFR is known to be present in the cartilage of other animals, it hadn't been studied in horses before. But researchers in her lab, including Wong, have now shown that it exists in horses, too.

Wong has spent the summer working in the lab, staining samples of cartilage taken from horses. She explains that the technique of H&E staining, using the dyes hematoxylin and eosin, allows her to see the structural elements of the cartilage and confirm characteristics of osteoarthritis.

Another stain called Safranin-O, Wong says, highlights the difference between healthy cartilage and tissue affected by osteoarthritis. The former shows up red and the latter blue. This method has a more experimental use because Wong has found that cartilage from osteoarthritic horses treated with TGF-α shows up red, meaning healthy.

"What I've observed so far has been pretty promising," Wong says. While this research is in vitro, Ortved says the next step would be to administer the treatment to horses with arthritis to see if it's as effective in vivo.

"Basically, everything I've learned in this lab is a new skillset, which is really exciting," Wong says, noting she had never done staining before. She also learned about the activation of the EGFR pathway as a potential way to limit osteoarthritis and about proteoglycan loss as an indicator of the disease. Wong says she connects this knowledge to more general information she has learned in classes at Penn, but this experience "puts me in a position where I can really understand it and see it in front of me."

Wong joins the lab's team meetings on Tuesdays and Fridays, an opportunity for her to share her findings. She has also had the chance to ask questions and to speak with other lab members about their career experiences.

"Now I'm a lot more open to exploring what veterinary medicine has to offer and what kinds of careers I could pursue," she says. While she is still interested in clinical practice, she is now considering doing research on the side.

"PURM-and any program that supports students at a younger timeline in their education-can be super effective at encouraging people to consider research, potentially go into research, or even just have that fundamental background on what research is," Ortved says. "I think that it can significantly affect how people feel about research and potentially even the trajectory of their careers."