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Osteoblasts are specialised bone cells responsible for building and regenerating bone tissue. Researchers at Leipzig University have shown in a high-profile study that a specific receptor plays a key role in the strength of bone cells – and how this receptor can be selectively activated. These findings could pave the way for the development of new medications with fewer side effects to help strengthen bones and muscles in ageing patients. The fundamental research has been published in the Nature journal Signal Transduction and Targeted Therapy.
There is a high demand for safe and long-lasting medications to treat bone loss, known medically as osteoporosis. In Germany, around six million people – mostly women – are affected by this widespread condition. Discovering new targets for drug development is therefore a key step towards better therapies with fewer side effects. The adhesion G protein-coupled receptor GPR133 belongs to a still relatively unexplored group of receptors. In a recent study, scientists at Leipzig University demonstrated that GPR133 plays a central role in building and maintaining healthy bone.
“If this receptor is impaired by genetic changes, mice show signs of loss of bone density at an early age – similar to osteoporosis in humans. Using the substance AP503, which was only recently identified via a computer-assisted screen as a stimulator of GPR133, we were able to significantly increase bone strength in both healthy and osteoporotic mice,” explains Professor Ines Liebscher, lead investigator of the study from the Rudolf Schönheimer Institute of Biochemistry at the Faculty of Medicine.
In bone tissue, GPR133 is activated through the interaction of neighbouring bone cells and mechanical strain. This triggers a signal that stimulates bone-forming cells (osteoblasts) and inhibits bone-resorbing cells (osteoclasts). The result: stronger, more resilient bones. The new active substance AP503 can mimic this natural activation. In the future, it could be used both to further strengthen healthy bones and to rebuild weakened ones – for instance, in cases of osteoporosis in women going through menopause.
Great potential for an ageing population
In an earlier study, researchers at Leipzig University had already found that activation with AP503 also strengthens skeletal muscle. “The newly demonstrated parallel strengthening of bone once again highlights the great potential this receptor holds for medical applications in an ageing population,” says Dr Juliane Lehmann, lead author of the study and a researcher at the Rudolf Schönheimer Institute of Biochemistry. The Leipzig research team is already working on several follow-up projects to explore the use of AP503 in various diseases and to further investigate the role of GPR133 in the body.
Background
For more than ten years, the study of adhesion G protein-coupled receptors has been a key focus at Leipzig University within Collaborative Research Centre 1423, Structural Dynamics of GPCR Activation and Signaling. Internationally, Leipzig is regarded as a leading centre in this field of research.
Translation: Matthew Rockey
Prof. Dr. Dr. Ines Liebscher
Universität Leipzig
Rudolph-Schönheimer-Insitut für Biochemie
Telephone: 0341 - 97 22141
Mail: Ines.Liebscher@medizin.uni-leipzig.de
Original publication in Signal Transduction and Targeted Therapy: The mechanosensitive adhesion G protein-coupled receptor 133 (GPR133/ADGRD1) enhances bone formation. https://doi.org/10.1038/s41392-025-02291-y
Professor Ines Liebscher
Source: private
Copyright: Leipzig University
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Professor Ines Liebscher
Source: private
Copyright: Leipzig University
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