Osteoporosis is a chronic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, leading to increased bone fragility and fracture risk. It develops when bone resorption outpaces bone formation, a process that commonly accelerates with aging, hormonal changes, and reduced mechanical loading. Credit: Shutterstock
Scientists uncovered how the protein Piezo1 translates physical activity into stronger bones, offering a path to exercise-mimicking therapies.
Scientists from the Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine at the University of Hong Kong (HKUMed) have identified a biological process that explains how exercise helps keep bones strong. The discovery could lead to new treatments for osteoporosis and bone loss in people who are unable to be physically active.
The researchers found a protein that functions as the body’s ‘exercise sensor’, translating physical movement into signals that protect bone health. This insight points to the possibility of developing drugs that reproduce the effects of exercise, which could benefit older adults, bedridden patients, and people with chronic illnesses who face an elevated risk of fractures. The findings were published in the journal Signal Transduction and Targeted Therapy.
“Osteoporosis and age-related bone loss affect millions worldwide, often leaving elderly and bedridden patients vulnerable to fractures and loss of independence,” said Professor Xu Aimin, Director of the State Key Laboratory of Pharmaceutical Biotechnology and Chair Professor in the Department of Medicine, School of Clinical Medicine, HKUMed, who led the study.
“Current treatments rely heavily on physical activity, which many patients simply cannot perform. We need to understand how our bones get stronger when we move or exercise before we can find a way to replicate the benefits of exercise at the molecular level. This study is a critical step towards that goal.”
HKUMed uncovered the mechanism behind bone strength, paving the way for novel osteoporosis treatment. The research was led by Professor Xu Aimin (second right) and Dr Wang Baile (second left, front row) from the Department of Medicine, the School of Clinical Medicine, HKUMed. Credit: The University of Hong Kong
Activating the bone’s ‘exercise sensor’ to reduce fat and build new bone
The World Health Organization estimates that about 1 in 3 women and 1 in 5 men over the age of 50 experience a fracture caused by weakened bones. The issue is particularly serious in Hong Kong as the population grows older, with osteoporosis affecting 45% of women and 13% of men aged 65 and above. Fractures linked to osteoporosis often result in lasting pain and disability, reducing independence and quality of life while also placing substantial strain on healthcare systems and the broader economy.
As people age, bones naturally lose strength, becoming thinner and more porous over time. Within the bone marrow, mesenchymal stem cells can develop into either bone-forming cells or fat cells. These stem cells respond strongly to external influences such as physical activity and mechanical pressure. With aging, however, they are more likely to become fat cells. As fat builds up in the bone marrow, it crowds out healthy bone tissue, weakens the skeleton further, and creates a downward cycle of bone loss that current treatments struggle to reverse.
When activated by physical activity, Piezo1 protein can reduce fat accumulation in the bone marrow and promote the formation of new bone. Credit: The University of Hong Kong
By studying mouse models alongside human stem cells, the researchers identified a key ‘switch’ known as Piezo1, a protein located on the surface of mesenchymal stem cells in the bone marrow. Piezo1 functions as an exercise sensor, detecting mechanical signals generated by movement that help maintain bone strength and reduce age-related frailty. In mice, activating Piezo1 through physical activity limited fat buildup in the bone marrow and promoted the creation of new bone.
When the protein was absent, the opposite occurred, with stem cells shifting toward fat accumulation and accelerating bone loss. The lack of Piezo1 also increased the release of specific pro-inflammatory signals (Ccl2 and lipocalin-2), which further pushed stem cells toward becoming fat cells and interfered with bone formation. The researchers found that blocking these signals could help restore healthier bone development.
Mimicking exercise for individuals with limited mobility
“We have essentially decoded how the body converts movement into stronger bones,” said Professor Xu Aimin. “We have identified the molecular exercise sensor, Piezo1, and the signalling pathways it controls. This gives us a clear target for intervention. By activating the Piezo1 pathway, we can mimic the benefits of exercise, effectively tricking the body into thinking it is exercising, even in the absence of movement.”
The research team identified clear intervention targets for treating osteoporosis, aiding in the development of drugs that simulate the benefits of exercise. This provides the potential for targeted treatments for vulnerable groups, such as those who are bedridden or have limited mobility, offering benefits comparable to those of physical activity. Credit: The University of Hong Kong
Dr Wang Baile, Research Assistant Professor from the same department, who co-led the research, added, “This discovery is especially meaningful for older individuals and patients who cannot exercise due to frailty, injury, or chronic illness. Our findings open the door to developing ‘exercise mimetics’ — drugs that chemically activate the Piezo1 pathway to help maintain bone mass and support independence.”
“This offers a promising strategy beyond traditional physical therapy,” remarked Professor Eric Honoré, Team Leader at the Institute of Molecular and Cellular Pharmacology, French National Centre for Scientific Research, who co-led the research. “In the future, we could potentially provide the biological benefits of exercise through targeted treatments, thereby slowing bone loss in vulnerable groups such as the bedridden patients or those with limited mobility, and substantially reducing their risk of fractures.”
The research team is now working to translate these findings into clinical applications, with the goal of developing new treatments to preserve bone health and improve the quality of life for an aging population and those confined to bed.
Reference: “Piezo1 activation suppresses bone marrow adipogenesis to prevent osteoporosis by inhibiting a mechanoinflammatory autocrine loop” by Baile Wang, Jie Liu, Qin Wang, Malika Arhatte, Lai Yee Cheong, Edyta Glogowska, Xue Jiang, Sookja Kim Chung, Leigang Jin, Qianxing Hu, Yu Wang, Eric Honoré and Aimin Xu, 28 October 2025, Signal Transduction and Targeted Therapy.
DOI: 10.1038/s41392-025-02455-w
This research was supported by the Areas of Excellence Scheme, and the General Research Fund of the Research Grants Council; the Health and Medical Research Fund under the Health Bureau, the Government of the Hong Kong Special Administrative Region of the People’s Republic of China; National Key R&D Program of China; the National Natural Science Foundation of China; the Human Frontier Science Program; the French National Research Agency; Fondation de France; Fondation pour la Recherche Médicale; and the Macau Science and Technology Development Fund.
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