For patients who have experienced severe trauma, burns, or major surgery, new bone grows instead of repaired muscle tissue. This condition, known as heterotopic ossification, not only causes intense pain but also leads to joint stiffness and lifelong functional impairment. Now, researchers at the University of Texas Southwestern Medical Center have finally uncovered the molecular mechanisms behind this mysterious phenomenon.

A research team led by Dr. Benjamin Levy of the center's organogenesis center has discovered that two key proteins—platelet-reactive proteins 1 and 2—play a crucial role in abnormal bone formation after trauma. This latest finding, published in the journal *Bone Research*, offers new hope for preventing this serious complication.

The research team discovered that when the body suffers trauma, TSP1 is mainly produced by immune cells (macrophages) that gather at the wound site, while TSP2 is secreted by mesenchymal progenitor cells at the edge of the injury. These two proteins work together to "remodel" the microenvironment of the damaged tissue: they rearrange the normally soft and elastic collagen fibers into a tight and rigid structure, which provides an ideal "scaffold" for the deposition of new bone.

To verify the key roles of these two proteins, researchers observed mice lacking both TSP1 and TSP2. The results showed that collagen fibers in the damaged tissues of these mice were disordered, failing to form the framework structure that supports bone growth, and thus the amount of abnormal bone formation was significantly reduced.

Even more encouragingly, researchers found that removing these two proteins only inhibited pathological bone growth without affecting normal bone development. This means that if targeted therapies against TSP1 and TSP2 can be developed in the future, it may be possible to precisely "remove" bone that shouldn't be growing without harming the healthy skeletal system.

The study also revealed an upstream regulator—the FUBP1 protein—that controls the production of TSP2. This discovery provides more potential targets for drug intervention.

“Heterostigmoid ossification can cause lifelong suffering for patients,” Dr. Levy said. “By revealing the central role of TSP1 and TSP2 in this process, we now have a clear therapeutic target. Our goal is to stop it before the abnormal bone causes permanent damage.”

Although current research is mainly based on animal models and further verification of its mechanism of action in humans is needed, this breakthrough undoubtedly brings new hope to patients suffering from heterotopic ossification.

About the University of Texas Southwestern Medical Center : The University of Texas Southwestern Medical Center is one of the leading academic medical centers in the United States, dedicated to advancing medical science through innovative research and clinical care.