A research team from Peking University Third Hospital, Department of Sports Medicine has discovered how physical activity helps relieve osteoarthritis (OA) – a painful joint disease affecting nearly 600 million people worldwide. Their study, published in Science Bulletin, shows that exercise enhances a natural “oxygen delivery system” using tiny vesicles released from red blood cells.
Osteoarthritis causes chronic pain and disability. Common painkillers like NSAIDs have side effects, especially in older adults. Exercise is known to improve symptoms, but the underlying mechanism has remained unclear. Cartilage and meniscus in joints lack direct blood supply and live in a constantly low‑oxygen environment. So how does movement bring more oxygen to these tissues?
The team found the answer in extracellular vesicles (EVs) derived from red blood cells. These nanoscale particles contain hemoglobin and can carry oxygen. Using electron microscopy and protein markers, the researchers identified these red‑blood‑cell EVs in human knee synovial fluid, cartilage, and meniscus. Importantly, plasma‑derived red blood cell EVs have a lower P50 (21.45 mmHg) than whole blood (53.65 mmHg), meaning they release oxygen under more hypoxic conditions – perfectly suited for the low‑oxygen joint environment.
How do these EVs penetrate the dense matrix of cartilage and meniscus? The study shows that a protein called histidine‑rich glycoprotein (HRG) on the EV surface binds strongly to heparan sulfate proteoglycans (HSPG) in the tissue matrix. This binding allows the EVs to be taken up by chondrocytes and meniscus cells mainly through macropinocytosis. The team also uncovered a “hypoxia call” system: low oxygen turns on HIF1α, which increases production of CXCL12. This chemokine then recruits oxygen‑carrying EVs via CXCR4 receptors on the EVs, guiding them exactly where they are needed.
Experiments in mice confirmed that physical activity is crucial. When mice moved freely, injected EVs accumulated in their knee joints. But when a leg was immobilized, EVs failed to reach the joint, and tissue hypoxia worsened. In porcine cartilage and meniscus, cyclic compression – like walking – significantly increased EV penetration and retention. Joint fluid viscosity drops with movement (shear thinning), further helping EVs reach target cells.
The researchers therefore propose a “circulation‑joint transport axis”: exercise drives red blood cell EVs from the bloodstream into the joint, where they deliver oxygen, relieve hypoxia, and maintain joint health. This work not only explains why exercise benefits osteoarthritis but also opens the door to non‑pharmacological, real‑time monitored therapies. Future efforts may combine wearable sensors with personalized exercise prescriptions to help patients manage arthritis without drugs.
About the institution:
The Department of Sports Medicine at Peking University Third Hospital, also known as the Institute of Sports Medicine of Peking University, was established in January 1959. It is the earliest and only comprehensive sports medicine institute in China that integrates precision clinical care, education, scientific research, and on‑site service for athletic teams. Over the past 66 years, the Department has grown into the largest and most influential sports medicine institute in China, covering four specialized fields: sports traumatology, sports rehabilitation, sports nutrition, and athletic supervision, with four clinical subspecialties in knee, hip, shoulder‑elbow, and foot‑ankle surgery. Recognized as a National Key Discipline by the Ministry of Education and designated as the exclusive Athlete Injury Prevention and Treatment Center by the Chinese Olympic Committee and the General Administration of Sport of China, the Department has provided medical support for Olympic and Winter Olympic Games. To date, it has treated over 380,000 athletes, including nearly 7,000 national team members, and has helped more than 200 athletes return to competition and win world championships. In 2026, the Department continued to serve as a key medical support unit for the Milan‑Cortina Winter Olympics, safeguarding Chinese athletes including gold medalist Xu Mengtao. The Department also houses the Beijing Key Laboratory of Research and Translation for Drugs and Medical Devices in Precision Diagnosis and Treatment of Sports Injuries, Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, China.
Science Bulletin
Experimental study