Osteoblasts are specialized bone cells that are responsible for the formation and regeneration of bone. In a high-ranking published study, researchers at Leipzig University have shown that a specific receptor is responsible for the strength of bone cells and how it can be specifically activated. The findings may help to develop new drugs with fewer side effects in the future to strengthen bones and muscles in ageing patients. The scientific work from the basic research has now been published in the Nature journal "Signal Transduction and Targeted Therapy".
There is a great need for safe and effective long-term medication to combat bone loss, known as osteoporosis. In Germany, around six million people, mainly women, are affected by this widespread disease. The discovery of new drug targets is therefore the basis for better therapies with fewer side effects. The adhesion G protein-coupled receptor GPR133 belongs to a group of receptors that has been little researched to date. In a recent study, scientists at Leipzig University were able to show that GPR133 plays a central role in the formation and maintenance of healthy bones.
if this receptor is disrupted by genetic changes, mice develop signs of bone loss at a young age - similar to osteoporosis in humans. Using the substance AP503, which was only recently identified as a stimulator of GPR133 on the basis of a computer-aided screen, it was possible to significantly increase bone strength in both healthy and osteoporotic mice," says Ines Liebscher, head of the study from 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-building cells (osteoblasts) and inhibits bone-degrading cells (osteoclasts). The result: stronger, more resistant bones. The new active ingredient AP503 can mimic this natural activation. In future, this could be used to further strengthen healthy bones as well as rebuild weakened bones - such as those affected by osteoporosis in menopausal women.
Great potential for an ageing population
In a previous study, the researchers at Leipzig University found that activation with AP503 also strengthens skeletal muscles. "The parallel strengthening of the bones that has now been shown once again proves the great potential that this receptor has in medicine for ageing people," says Juliane Lehmann, first author The Leipzig scientists are already working on several follow-up projects to investigate the use of AP503 in various diseases and to further elucidate the role of GPR133 in the organism.
Background
For more than ten years, the investigation of so-called adhesion G protein-coupled receptors in the Collaborative Research Center 1423 "Structural Dynamics of GPCR Activation and Signal Transduction" has been an important focus at Leipzig University. Internationally, Leipzig is regarded as a leading center in this field of research.
Original publication in Signal Transduction and Targeted Therapy : The mechanosensitive adhesion G protein-coupled receptor 133 (GPR133/ADGRD1) enhances bone formation. Doi: https://doi.org/10.1038/s41392-025-02291-y
