The School of Chinese Medicine (SCM) recently completed a joint translational study on therapeutic non-coding RNA with bone anabolic potential in collaboration with the State Key Laboratory of Fundamental and Applied Studies in Aerospace Medicine of the China Astronaut Center. The research identifies a novel therapeutic target with bone anabolic potential in clinical bone specimens, evidenced by successfully revising bone loss in osteoporotic animal models. The findings provide an important foundation for developing novel RNA-interference-based drugs to treat bone diseases that involve impaired bone formation. The research paper “miR-214 targets ATF4 to inhibit bone formation” was published in the latest issue of Nature Medicine, the premier scientific journal for biomedical research. In the initial stages of the research, the team conducted a systemic screening of the bone specimens collected through a number of clinical centres and identified a novel microRNA (a type of non-coding RNA), which is highly correlated with bone formation. The Beijing group, led by Dr. Li Yingxian, then investigated the effect of the identified microRNA on osteoblastic function and explored the underlying mechanism in vitro. The HKBU group went on to translate the therapeutic target with bone anabolic potential to animal studies using the bone-targeted siRNA delivery system and successfully reversed bone loss in an osteoporotic animal model. They further explored the pathophysiological mechanism of reduced bone formation during aging. It is hoped that these research findings would lead to the development of RNA-interference-based bone anabolic drugs capable of reversing bone loss during aging. This would constitute a big step forward in resolving the tough issue of age-related bone loss in clinical medicine. The microRNA identified, the first therapeutic molecular target originating from human bone specimens, is of great significance in clinical medicine. Based on the model of translational medicine, the Hong Kong-Beijing team integrated research on molecular target identification, drug delivery as well as treatment validation in a systematic way and set a successful model for collaborative research in basic and clinical disciplines. According to Dr. Zhang Ge, Associate Professor of the Teaching Division of SCM, who is the corresponding author of the research paper, only less than 2% of the genes in the human genome are coding genes, whereas the remaining 98% are non-coding genes. The function of these non-coding genes was unknown and they were considered as “dark material” or “rubbish DNA”. However, new data from the Encyclopedia of DNA Elements (ENCODE) show that these “rubbish genes” in the human genome are in fact responsible for the regulation of genetic function and might be even more important than the conventional coding genes. Dr. Zhang Ge said: “Our findings have decoded the function of one kind of this ‘dark material’ but it is believed to be just the tip of the iceberg. We are working out specific research on developing alternative bone anabolic drugs with therapeutic candidates, including the useful molecular material from natural herbs. There is an interesting journey ahead with a lot of unsolved mysteries. We need to strengthen our team and recruit more talent from different disciplines to drive multidisciplinary research collaboration.” This research achievement is supported by the newly established Institute for Advancing Translational Medicine in Bone & Joint Diseases of HKBU. Professor Lu Aiping, Dean of SCM and Director of the Institute, said that it was a platform for translational medicine research in bone and joint diseases jointly set up by SCM and the University’s Faculty of Science on the initiation of SCM. With the coming together of scientists from different disciplines, including Dr. Guo Baosheng, a young and promising scientist of SCM who is one of the co-first authors of the research paper, the Institute has launched a number of cutting-edge multi-disciplinary research projects. Professor Lu said that a larger scale integration of research resources was underway with a view to attracting more outstanding young researchers with a multi-disciplinary background. For details of the paper, please visit website: http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3026.html.
Professor Albert Chan (third from left), Professor Lu Aiping (sixth from left), and members of the SCM management share the joy of Dr. Zhang Ge (fifth from left) and his research team