Researchers show how damaged tissue remodels, causing painful bone formation in muscles and tendons
China, February 9, 2026 /EINPresswire.com/ — Heterotopic ossification (HO) is an atypical bone formation that causes chronic pain and affects patients’ quality of life. It occurs in regions rich in extracellular matrix (ECM) derived from mesenchymal progenitor cells (MPCs). Thrombospondins 1 and 2 are important regulators of the ECM, but their roles in MPC/ECM interaction and H2O formation remain unclear. Researchers have now uncovered the role of these proteins in damage repair and HO formation and found that blocking these proteins may help prevent HO.
After a serious injury, burn, fracture, or major surgery, the body normally repairs damaged tissue and restores movement. However, in some patients, the healing process takes an unexpected and harmful turn. Instead of rebuilding healthy muscles and tendons, new bone begins to form inside the soft tissue, causing pain, stiffness, and long-term disability. This condition, known as heterotopic ossification (HO), often develops after trauma, joint replacement surgery, or combat-related injuries and may require additional surgery. Despite its profound impact on patients’ lives, the biological processes behind it are poorly understood.
In a new study, a research team led by Dr. Benjamin Levi of the Center for Organogenesis at the University of Texas Southwestern (USA) has revealed how two important proteins, thrombospondin 1 (TSP1) and thrombospondin 2 (TSP2), contribute to abnormal bone growth after injury by remodeling damaged tissue. The findings help explain how damaged tissue is “reprogrammed” to support bone formation and suggest new ways to prevent this serious complication. The study was published in the journal Volume 14. Journal “Born Research” January 19, 2026.
“Our research shows that these proteins play a central role in shaping the healing environment after injury. When their activity is reduced, abnormal bone growth is dramatically reduced,” Dr. Levi says.
Previous studies have suggested that changes in the extracellular matrix (ECM) can influence how tissues heal. However, the molecular signals guiding these changes were unknown. The new study aimed to identify the specific factors that shape this healing environment after injury.
To investigate this, the researchers used an established mouse model that involves burns and tendon injuries, a type of trauma known to trigger HO. The team then used advanced genetic and imaging tools to track how the cells and tissues changed over time. They combined several techniques, including single-cell RNA sequencing and spatial transcriptomics. Furthermore, we used high-resolution imaging to analyze collagen fibers and 3-dimensional scanning to analyze bone formation.
The analysis showed that TSP1 is primarily produced by immune cells known as macrophages at the center of injuries, and lower levels were also detected in mesenchymal progenitor cells (MPCs), early-stage cells that can develop into bone-forming cells. In contrast, TSP2 was mainly produced by MPCs near the edges of the damaged area.
The researchers also discovered that these proteins influence the arrangement of collagen fibers. During normal healing, collagen is flexible and loosely organized. In injured tissues with active thrombospondin signaling, fibers aligned tightly and formed structures that supported bone growth. To find out whether these proteins are essential, the researchers studied mice lacking both TSP1 and TSP2. In these animals, collagen fibers were disorganized and abnormal bone growth was significantly reduced.
“When both proteins were removed, the tissue no longer formed the supportive framework necessary for ectopic bone development, resulting in a significant reduction in harmful bone formation,” Dr. Levi says.
Scans confirmed that these mice had much smaller bone deposits in their tendons and surrounding tissues, while their normal skeleton was unaffected. This suggests that targeting these proteins may reduce abnormal bone growth without interfering with healthy bone development.
The study also identified a regulatory protein called FUBP1 that helps control TSP2 production. When FUBP1 levels decreased in cells grown in the lab, TSP2 levels also decreased, weakening the signals that promote tissue remodeling. Additionally, the authors caution that their findings are primarily based on animal models. Further research is needed to see if the same mechanism works in humans and how safely humans can be targeted. Taken together, this study provides insight into how thrombospondin signaling contributes to HO after injury.
“HO can be life-changing for many patients. By understanding the role of TSP1 and TSP2 in HO formation, we hope to develop treatments that target these proteins and prevent HO before it causes permanent damage,” concludes Dr. Levi.
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reference
Original paper title: Thrombospondins 1 and 2 regulate mesenchymal progenitor cell fate and stromal organization
Journal: Bone Research
Doi: 10.1038/s41413-025-00493-2
About the University of Texas Southwestern
The University of Texas Southwestern is one of the nation’s premier academic medical centers, combining pioneering biomedical research with outstanding clinical care and education. The institution’s faculty have won six Nobel Prizes, including 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute investigators. Our more than 3,200 full-time faculty members are responsible for groundbreaking medical advances and are committed to rapidly translating science-driven research into new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits annually.
Website: https://www.utsouthwestern.edu/about-us/
About Dr. Benjamin Levi of the University of Texas Southwestern
Dr. Benjamin Levi is a professor at the University of Texas Southwestern Center for Organogenesis, where he holds the Dr. Lee Hudson and Dr. Robert R. Penn Department of Surgery Chair and Chief of Burn, Trauma, and Acute and Critical Care Surgery. He earned his medical degree from Northwestern University and completed surgical residencies at the University of Michigan, Stanford University, and Massachusetts General Hospital. With over 15 years of research experience and over 100 publications, his research focuses on heterotopic ossification, tissue regeneration, stem cell biology, and wound healing.
Funding information
This research was supported by Department of Defense grants HT9425-23-1-0327 and National Institutes of Health R01AR078324.
Eni Bao
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