The ability to control whether certain stem cells ultimately become bone cells holds great promise for regenerative medicine and potential therapies aimed at treating metabolic bone diseases. Now, University of California, Los Angeles, (UCLA) School of Dentistry professor and leading cancer scientist Cun-Yu Wang, D.D.S., Ph.D., and his research team have made a significant breakthrough in that direction. The scientists have discovered two key epigenetic regulating genes that govern the cell-fate determination of human bone marrow stem cells.
Dr. Wang's new research was featured on the cover of the July 6 issue of Cell Stem Cell , the affiliated journal of the International Society for Stem Cell Research. The groundbreaking study grew out of Dr. Wang's desire to better understand the epigenetic regulation of stem cell differentiation, in which the structure of genes is modified while the sequence of the DNA is not. Dr. Wang and his team found that KDM4B and KDM6B, two gene-activating enzymes, can promote stem cells' differentiation into bone cells by removing methyl markers from histone proteins. This process occurs through the activation of certain genes favoring a commitment to one lineage and the concurrent deactivation of genes favoring other lineages.
The findings imply that chemical manipulation of these gene-activating enzymes may allow stem cells to differentiate specifically into bone cells, while inhibiting their differentiation into fat cells. The group's research could pave the way toward identifying potential therapeutic targets for stem cell–mediated regenerative medicine, as well as the treatment of bone disorders like osteoporosis, the most common type of metabolic bone disease.
”Through our recent discoveries on the lineage decisions of human bone marrow stem cells, we may be more effective in utilizing these stem cells for regenerative medicine for bone diseases such as osteoporosis, as well as for bone reconstruction,” Dr. Wang says.
”The discovery that Dr. Wang and his team have made has considerable implications for craniofacial bone regeneration and treatment for osteoporosis,” says No-Hee Park, D.M.D., Ph.D., Dean of the School of Dentistry. ”As a large portion of our population reaches an age where osteoporosis and gum disease could be major health problems, advancements in aging-related treatment are very valuable.” The study was supported by grants from the National Institute of Dental and Craniofacial Research.