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Study links gene defect and increased osteoporosis risk
Discovery of trigger mechanism for CB2 gene receptor may yield better diagnosis and treatment, researcher says.
Researchers found a connection between a defective gene receptor, bone loss and high osteoporosis risk. Stimulating the receptor may slow bone loss, they said.
Itai Bab, DMD, chief of the bone laboratory at Hebrew University of Jerusalem, conducted the study with Meliha Karsak, PhD, a molecular biologist at the University of Bonn, Germany, conducted the study with colleagues at the two universities as well as at centers in the United States, the United Kingdom and France.
Karsak and colleague Orr Ofek, BmedSc, also of the Hebrew University of Jerusalem, won the German Society for Endocrinology’s CHRUKS Osteology Prize in recognition of their and their colleagues’ findings. The study has appeared in the journals Human Molecular Genetics and Proceeding of the National Academy of Sciences.
COURTESY: HEBREW UNIVERSITY OF JERUSALEM |
The researchers performed an animal study using mice and in vitro human gene testing. They cited two cannabinoid receptor types that the body produces: CB1 and CB2. The first type comprises nerve cells in the brain and is responsible for the psychological effect of cannabis, among other things. The second type does not appear in nerve cells and its function was unknown. To identify its function, the researchers “switched off” the animals’ CB2 receptors. The results pointed toward a CB2-bone density connection, Bab and Karsak said.
“The animals gradually lost their stabilizing trabeculae,” they said. “We found in these mice that the number of osteoclasts — special cells that can break down the bone tissue — increases by almost 50%.”
Further research showed that osteoclasts and their biological counterparts, osteoblasts, which form bone tissue, both carry CB2 receptors, Bab said.
Reducing bone loss
Additional experiments supported the researchers’ theory about the receptors. The researchers removed the ovaries of several mice. Then, expecting the resulting estrogen deficiency to cause bone loss and osteoporosis, they gave the mice an active substance that bonds to the CB2 receptor. The experiment minimized bone loss, despite the lack of estrogen.
“In this way we were able to diminish the bone loss caused by ovary removal,” Bab said.
Karsak and her team aimed to apply the study to humans. They consulted with scientists working in France who had access to genetic samples from 160 osteoporotic women and 240 healthy women. Karsak found that a specific CB2 mutation was more common among the osteoporosis patients than among the healthier control group.
People with the genetic defect are not “destined” to suffer bone loss or osteoporosis, Karsak said. However, “Women with this mutation have a three-fold higher risk of osteoporosis,” she added.
Study results may help predict and prevent osteoporosis, and lead to better diagnoses and treatments, Karsak said.
“In many women with osteoporosis the CB2 receptor functions, so in their cases the disease has other causes,” she said. “For them we could consider stimulating the receptor through medication and in this way slow down their bone loss.”
The experiments showed potential success — and hope for women with a CB2 defect.
“First, it is easy to identify whether a woman is carrying the relevant mutation, so the results promise improved and faster diagnosis,” the authors said. “Second, they have drawn attention to a previously unknown regulatory mechanism, making it a focus of osteoporosis research. Here lies the chance of developing new medicines in the long term.”
The Bikura (First) Program of the Israel Science Foundation and U.S. National Institutes of Health funded the study.
For more information:
- Ofek O, Karsak M, Leclerc N, et al. Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc Natl Acad Sci USA. 2006;103:696-701.