Exercise as medicine—how exercise protects joints in aging-related osteoarthritis
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Researchers at Mass General Brigham have found that moderate-intensity exercise alters circulating extracellular vesicles in ways that promote cartilage health and tissue resilience, identifying microRNA-29 as a key mediator that improved characteristics of aged cartilage cells and reduced signs of joint degeneration.
Published in Nature Aging, the findings provide new insight into how exercise protects joints and could inform future osteoarthritis treatments designed to reproduce exercise's beneficial biological effects for patients who cannot exercise sufficiently. Hirotaka Iijima, Ph.D., PT, and Fabrisia Ambrosio, Ph.D., MPT, of the Discovery Center for Musculoskeletal Recovery within the Department of Physical Medicine and Rehabilitation at Mass General Brigham, are the lead and senior authors of the paper.
The biological gap behind exercise benefits
Osteoarthritis is one of the leading causes of pain, disability and loss of mobility among older adults worldwide. While regular exercise is strongly recommended for people with osteoarthritis and is known to protect joint tissue, we still do not fully understand the biological mechanisms behind this protection. A better understanding of how exercise provides this benefit will help us develop interventions and therapies that reproduce its effects, especially for patients who face barriers to exercising regularly.
The research team wanted to understand whether circulating extracellular vesicles (EVs)—nanoparticles released by cells into the bloodstream—help mediate the protective effects of exercise on joint health. Specifically, they investigated whether exercise alters the molecular cargo carried by EVs and whether these changes can directly improve cartilage health in aging and osteoarthritic joints.
Tracing exercise signals through vesicles
The approach spanned EV analyses, cell culture experiments, mouse studies of aging-associated osteoarthritis and human exercise interventions.
In the human portion of the study, older adults participated in a structured aerobic exercise program, and the researchers collected blood samples before and after three months of training. Using these samples, they analyzed how aerobic exercise altered the molecular contents of circulating EVs and evaluated the biological effects of these exercise-derived EVs on cartilage cells and joint tissues. The study also identified and tested specific molecules enriched in EVs after training.
Exercise reshapes cartilage-protective cargo
The team found that moderate-intensity exercise significantly changed the molecular cargo of circulating EVs in ways that promoted cartilage health and tissue resilience. Specifically, EVs collected after exercise improved the health of cells and cartilage tissue in the knee joint.
Among the molecular signals enriched after exercise, they identified microRNA-29 as a key mediator of the beneficial effects. Delivery of microRNA-29 to aged osteoarthritic joints restored more youthful characteristics in cartilage cells and reduced features associated with joint degeneration.
The findings provide new insight into how exercise promotes joint health and help explain why physical activity is beneficial for people with osteoarthritis. By identifying specific biological signals altered by exercise, this work brings us closer to understanding the molecular pathways underlying rehabilitation interventions.
Potential treatments for patients with limited mobility
These discoveries may inform the development of new treatments for osteoarthritis, including therapies that use EVs or their molecular cargo. Such strategies could be especially valuable for people who are unable to get sufficient physical activity because of pain, disability or other health limitations. They also show how regenerative medicine can be paired with traditional rehabilitation principles and approaches.
The researchers anticipate that this work will help guide the design of clinical programs focused on maximizing the biological responses associated with joint protection and tissue health.
As physical therapists, the researchers are motivated by a simple but important question: Why and how does exercise work? While there is much left to learn about why it's one of the most effective treatments for a variety of musculoskeletal conditions, this study represents an important step forward in our collective knowledge.
Publication details
Hirotaka Iijima et al, Exercise enhances aged chondrocyte health through microRNA-29-enriched extracellular vesicles, Nature Aging (2026). DOI: 10.1038/s43587-026-01225-9
Journal information: Nature Aging
Key medical concepts
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PhysiatryFitness & Physical activityOrthopedicsHealthy agingCommon illnesses & Prevention Provided by Mass General Brigham Who's behind this story?
Gaby Clark
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