A research team led by Prof. Liu Mingyao and Prof. Luo Jian at ECNU’s Institute of Biomedical Sciences, and the research team of Chief Physician Xiao Jianru at Shanghai Changzheng Hospital attached to China’s Second Military Medical University (SMMU) have jointly found that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) is another receptor for RANKL and can negatively regulates osteoclast differentiation and bone resorption. That may provide new effective treatment to orthopedic diseases.
The research results were published online by Nature Medicine, a monthly peer-reviewed medical journal, on April 13, 2016. Luo Jian and PhD. candidate Yang Zhengfeng of ECNU are paralleled first authors of the paper. Liu Mingyao, Luo Jian and Xiao Jianru are parallel corresponding authors. The research team of Academician Ning Guang at Shanghai Ruijin Hospital and some Austrian scientists have also participated in some parts of the research.
Prof. Luo Jian
With the acceleration of social aging, people with osteoporosis and bone tumors is increasing. However, the clinical understanding and treatment of these diseases are still quite inadequate. To change this situation, Prof. Liu Mingyao, Prof. Luo Jian and their teammates have carried systemic research on bone tumors, osteoporosis, and other orthopedic diseases and have made various world-class scientific achievements.
In 2013, the Institute of Biomedical Sciences at ECNU and SMMU’s Shanghai Changzheng Hospital, which is very famous for its orthopedics treatment, established the ECNU and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology. After a three-year construction, the joint research center has developed into an orthopedic oncology research center standing infirst class research in China, and famous around the world.
In the past three years, the joint research center has won two State key programs of Natural Science Fund of China (NSFC), two major research programs of Shanghai Science & Technology Commission and Shanghai Municipal Commission of Health and Family Planning, publishing more than 10 research papers on the world’s top level academic journals including Nature Medicine, Nature Communication, PANS, and J Am Chem Soc, and authorized two national invention patents.
Prof.Liu Mingyao, Prof.Luo Jian and their team members.
Both the research team of Liu Mingyao and Luo Jian, and the Stefansson research team in Europe have demonstrated that LGR4 plays an important role in the regulation of osteoporosis in their early work. However, the molecular mechanism of LGR4 in the regulation and whether LGR4 can be used as a drug target are still unclear.
In the latest research, Liu Mingyao and Luo Jian’s team worked jointly with Xiao Jianru’s team and continued on in-depth research in this topic. They found that LGR4 is another receptor for tumor necrosis factor super family member 11 (TNSF11, also known as RANKL) and developed a new protease inhibitor using LGR4 as the drug target. Their experiments show that the protease inhibitor can significantly inhibit orthopedic diseases including osteoporosis and bone tumors.
The research paper has won high evaluation from international reviewes. Quite a few journals including BioCentury Innovations, an electronic journal of the Nature Publishing Group, has shown great interest in this research and will highlight it in the journal. What’s more, the research results have been applied for the national invention patents and some biopharmaceutical companies have also shown interest in this research results. Subsequent research and products development are in progress.
