Scientists Identify Bone-Building Receptor That Could Fight Osteoporosis

Scientists at Leipzig University have identified a receptor called GPR133 that appears to play an important role in keeping bones strong, offering a potential new target for osteoporosis treatment. Osteoporosis, which weakens bones and raises the risk of fractures, affects millions of people worldwide — in Germany alone, about 6 million people, most of them women.

GPR133 belongs to a group of receptors known as adhesion G protein-coupled receptors, which sit on the surface of cells and help them respond to signals from their surroundings. This family of receptors is still not fully understood.

"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," said Professor Ines Liebscher, the study's lead investigator at Leipzig's Rudolf Schönheimer Institute of Biochemistry. "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."

Inside bone tissue, GPR133 responds to physical forces and interactions between nearby bone cells. Activating the receptor encourages the activity of osteoblasts, the cells that build new bone, while reducing the activity of osteoclasts, which remove old bone — shifting the balance toward stronger, more durable bone. One potential application is osteoporosis linked to menopause, when declining hormone levels can accelerate bone loss.

An earlier Leipzig study had already found that 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 aging population," said Dr. Juliane Lehmann, the study's lead author. The team is now investigating whether AP503 has applications in other diseases.