Scientists May Have Found a Way to Strengthen Bones for Life

There is a high demand for safe and long-acting drugs to treat bone loss, medically known as osteoporosis. In Germany, around six million people—mostly women—are affected by this widespread disease, and worldwide, around 32 million people suffer from it. The discovery of new approaches to drug development is therefore an important step toward better therapies with fewer side effects.

Substance for Promoting Stronger Bones

The adhesion G protein-coupled receptor GPR133 belongs to a relatively unexplored group of receptors. In a recent study, scientists at the University of Leipzig have shown that GPR133 plays a central role in building and maintaining healthy bones. “When this receptor is impaired by genetic changes, mice show signs of bone density loss at an early age – similar to osteoporosis in humans. Using the substance AP503, which was recently identified as a stimulator of GPR133 through computer-assisted screening, we were able to significantly increase bone strength in both healthy and osteoporotic mice,” explains Professor Ines Liebscher, lead researcher of the study at the Rudolf Schönheimer Institute of Biochemistry at the Faculty of Medicine.

In bone tissue, GPR133 is activated by the interaction of neighboring bone cells and mechanical stress. This triggers a signal that stimulates bone-forming cells (osteoblasts) and inhibits bone-resorbing cells (osteoclasts). The result: stronger, more resistant bones. The new active ingredient AP503 can mimic this natural activation. In the future, it could be used both to further strengthen healthy bones and to rebuild weakened bones – for example, in cases of osteoporosis in menopausal women.

Great Potential for an Aging Population

In an earlier study, researchers at the University of Leipzig had already found that activation with AP503 also strengthens skeletal muscle. “The now proven parallel strengthening of bones once again underscores the great potential of this receptor for medical applications in an aging population,” says Dr. Juliane Lehmann, first author of the study and scientist at the Rudolf Schönheimer Institute for Biochemistry.

The Leipzig research team is already working on several follow-up projects to investigate the use of AP503 in various diseases and to further explore the role of GPR133 in the body. For more than ten years, research into adhesion G protein-coupled receptors has been a focus at the University of Leipzig as part of the Collaborative Research Center 1423 “Structural Dynamics of GPCR Activation and Signal Transduction.” Leipzig is internationally recognized as a leading center in this field of research.