F-Actin Protein Could Be Key for Osteoarthritis Prevention

Scientists at the University of Delaware (UD) have identified a protein – adseverin – that is protective against osteoarthritis (OA). The research, conducted in cartilage cell and animal models, is published in Science Advances.

Osteoarthritis currently lacks a cure

OA is the most prevalent form of arthritis and affects over 32.5 million Americans. Caused by the breakdown of articular cartilage, which provides cushioning for bone ends, it frequently occurs in the hands, knees or hips. OA can be incredibly painful and debilitating, and currently lacks a cure. Standard-of-care treatment options might include physical therapy, medications that target pain or surgery in worst case scenarios.

UD professor Dr. Justin Parreno was working on cartilage therapy when he observed that healthy cartilage cells expressed large amounts of a protein called adseverin. A former hockey player and now a dedicated basketball and weightlifting enthusiast, he has encountered his fair share of injuries in the past. “I’ve always been into the musculoskeletal system just because of sports. I think I was predisposed to orthopedic research because of that,” he says.

In the lab, Parreno and colleagues generated knockout mouse models lacking adseverin and discovered that articular chondrocyte function was compromised via a reduction in filamentous actin (F-actin). Chondrocytes are the only cell type in cartilage tissue, where they secrete a mélange of growth factors and enzymes to support extracellular matrix synthesis.

Parreno describes that F-actin acts as a “shield”, protecting cartilage cells from stress that occurs through joint movement. In animal studies, he discovered that loss of F-actin ultimately causes these cells to die. “The cells are really round, and you have F-actin around the cells,” he says.

“If you lose F-actin, those cells are sensitive because there is mechanical stress on them, and they will probably undergo death. Dead cells aren’t able to produce the molecules that are required to regenerate cartilage, and eventually the cartilage degrades. The cells that remain are also producing hypertrophic molecules resulting in mineralization and tissue stiffness, which leads to a really bad joint,” Parreno adds. In adseverin knockout mice, these molecular changes made the articular cartilage weaker and enhanced OA severity in mice that underwent surgery to induce the condition.

Adseverin as a therapeutic target for OA?

At the Delaware Center for Musculoskeletal Research, Parreno is continuing to explore F-actin’s relationship to OA development. Currently, his lab is exploring another F-actin-binding protein called tropomyosin. “What I really find groundbreaking about this work is not necessarily adseverin, but that F-actin is reduced in OA and leads to all of these changes,” Parreno describes. “We know all of these changes are happening and if we can find out what’s the critical node in regulating all of these things, then we may be able to develop an OA therapy. I think targeting F-actin might be that and we have just uncovered the tip of the iceberg.”

It’s possible that other molecules – beyond adseverin – could regulate F-actin, potentially leading to novel therapeutic avenues for OA. “Once we figure out which molecules are important, perhaps we can chemically target them to prevent joint degradation,” Parreno says.

Reference: Chan B, Glogauer M, Wang Y, et al. Adseverin, an actin-binding protein, modulates hypertrophic chondrocyte differentiation and osteoarthritis progression. Sci Adv. 9(31):eadf1130. doi:10.1126/sciadv.adf1130

This article is a rework of a press release issued by the University of Delaware. Material has been edited for length and content.