Osteoarthritis - early diagnosis and new strategies

OSTEOARTHRITIS (OA), or osteoarthritis, is a chronic low-grade inflammatory disease that leads to the breakdown of joint cartilage and causes reduced mobility (disability) and severe pain. According to the World Health Organization, 10% of the world's population over the age of 60 has joint pain associated with osteoarthritis, which is serious because OA also increases the risk of cardiovascular disease, diabetes, and dementia. Similar acute traumatic osteoarthritis, which later in life leads to chronic joint pain, affects athletes and sport horses.

ONE OF THE BIGGEST PROBLEMS WITH OSTEOARTHRITIS is that the disease is not detected until the patient begins to feel pain, which usually occurs late in the course of the disease, when structural changes in the joints are evident and can be diagnosed with X-rays or magnetic resonance imaging (MRI). Since the damage to the joint cartilage at this stage is usually so severe that it cannot be cured, we need new methods to diagnose osteoarthritis at an earlier stage. Another challenge is that we currently lack drugs that can prevent or cure the disease. In addition to humans, osteoarthritis also affects horses with the same disease progression. The Food and Drug Administration (FDA) in the United States has recently approved and recommended horses as test animals for studying osteoarthritis in humans.

JOINT CARTILAGE IS COMPOSED of a complex protein structure, and sentinel cells in the joint capsule surrounding the joint are ready to be activated in the event of inflammation. In osteoarthritis, these sentinel cells are activated and produce inflammatory substances that can break down the protein structure in the cartilage and also spread the inflammation to the blood. When the proteins in the joint cartilage are broken down, small protein fragments are formed that leak from the joint into the blood (known as biomarkers), but the fragments can also enter and affect the biological activity of the cartilage cells (matrikines) in a way that is currently unknown. Inflammation also disrupts calcium signaling in cartilage cells, which is critical for them to function normally. We have recently identified drug substances that can restore calcium signaling in diseased cartilage cells and also cause the cells to reduce their production of inflammatory substances and substances that cause pain.

THE OBJECTIVE OF THIS PROJECT is to clarify the role of sentinel cells in the inflammation that initiates and drives osteoarthritis, and to develop knowledge that explains the biological function of cartilage fragments. Furthermore, we plan to use four different cartilage fragments that we have identified in the blood (biomarkers) of horses with osteoarthritis to identify different stages of the disease in horses and humans, with a focus on the early stages when the joint can still be healed. Using artificial intelligence and big data, we will then develop a biomarker panel for the purpose of early diagnosis, prognosis of joint damage, and evaluation of the effects of different treatments and rehabilitation programs. In this part of the project, blood samples from soccer players and racehorses, both of which often suffer from acute traumatic osteoarthritis, will be analyzed. As part of the project, we will also evaluate a new unique combination of drugs on cartilage cells from human patients in vitro, and conduct a clinical trial on horses in a randomized, double-blind, in vivo study.

OUR STRENGTH lies in close collaboration between equine and human studies, where experts from veterinary and human medicine work together with cell biologists and immunologists, as well as world-leading researchers in AI and the development of sophisticated sensors. Through this project, we will strengthen our collaboration and develop a new platform for disease-oriented research projects, which have great potential to contribute to improved health for both humans and horses over the long term. This interdisciplinary project, based on close collaboration between four universities, has great potential to solve the question of how osteoarthritis can be diagnosed and cured.