A new study points to a key bone-strengthening mechanism at work in the body, which could be targeted to treat the bone-weakening disease, osteoporosis.
The study, led by researchers from the University of Leipzig in Germany and Shandong University in China, identified the cell receptor GPR133 (also known as ADGRD1) as being crucial to bone density, via bone-building cells called osteoblasts.
Variations in the GPR133 gene had previously been linked to bone density, leading researchers to turn their attention to the protein it encoded.
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The team ran tests on mice in which the gene was either absent or could be activated using a chemical called AP503. In the absence of the GPR133 gene, the mice grew up with weak bones, resembling the symptoms of osteoporosis. However, when the receptor was present and activated by AP503, bone production and strength improved.
“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,” says University of Leipzig biochemist Ines Liebscher.
In these experiments, AP503 serves as a biological button that gets the osteoblasts working harder. The researchers were also able to show that it could work in tandem with exercise to strengthen bones even further.
Knowing that the GPR133 cell receptor is a crucial link in keeping mice bones strong is an important finding. While the results are based on an animal model, the underlying processes are likely similar in humans.
“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,” says Liebscher.
The researchers say future treatments could be used to strengthen bones that are already healthy, and build degraded bone back up to full strength, as in cases of osteoporosis in women who are going through menopause.
There are actually numerous factors that have an influence on bone strength, and that gives scientists plenty of scope for finding methods that ward off issues like osteoporosis and promote a healthier old age.
Osteoporosis is a serious condition affecting millions worldwide. While available treatments can slow the condition’s progress, there’s no way to reverse or cure the condition. Current treatments also tend to come with risky side effects (like an increased risk of other diseases) or become less effective over time.
“The newly demonstrated parallel strengthening of bone once again highlights the great potential this receptor holds for medical applications in an aging population,” says molecular biologist Juliane Lehmann, from the University of Leipzig.
The research has been published in Signal Transduction and Targeted Therapy.