Medical researchers at the University of Bonn, working in collaboration with scientists from Israel, the USA and Britain, have identified a previously unknown regulatory mechanism in the process of bone loss. Their findings could open up new approaches to the treatment of osteoporosis.
More than four million people, predominantly women, are estimated to suffer from this distressing illness in Germany alone. In recognition of the importance of her results, Dr. Meliha Karsak from the Bonn-based Life & Brain Center has recently been awarded the Osteology Prize of the German Society for Endocrinology, which entails a cash award of 8,000 euros. Her study will now be published in the renowned "Proceedings of the National Academy of Sciences" (PNAS).
Working together with colleagues from the University of Jeruslam, Dr. Meliha Karsak found that mice with a particular gene defect have a lower bone density. This breakthrough is making "cannabinoidreceptors" a key focus of osteoporosis research.
"We know two types of cannabinoidreceptors, CB1 and CB2," explains Dr. Karsak. "The CB1 receptor is formed by nerve cells in the brain and is responsible for, among other things, the mental effect of cannabis. The CB2 receptor, on the other hand, does not occur in nerve cells; its function was previously unknown." To explore this function the scientists working with Bonn's senior brain expert Professor Dr. Andreas Zimmer have made genetic modifications in mice in order to switch off their CB2 receptor. Dr. Karsak summarises what happened: "The animals gradually lost their stabilising trabeculae. We found in these mice that the number of osteoclasts – special cells that can break down the bone tissue –increases by almost 50 per cent."
Signal molecules regulate bone density
Together with a research group from Israel and England, Dr. Karsak was able to demonstrate that osteoclasts, as well as their opposite number, the osteoblasts, which are responsible for building bone, carry CB2 receptors on their surface. In this way it appears that signal molecules like the endocannabinoids being formed by the body are able to regulate bone growth.
This thesis has been supported by experiments on mice whose ovaries were removed. The resulting oestrogen deficiency would normally lead to a depletion of bone material and finally to "mouse osteoporosis". "We treated these mice with an active substance that bonds specifically to the CB2 receptor. In this way we were able to diminish the bone loss caused by ovary removal," explains the molecular biologist.
Many patients carry a particular variant of the CB2 gene