Generating Bone: Missing Link Found?

A team of scientists, led by researchers from the University of Southern California (USC), have identified a key action of a gene critical to bone formation and the evolution of vertebrates. This, say the scientists, is another step towards the goal of generating bone “de novo.”

According to the April 28, 2016 news release, “The Sp7 or Osterix gene more than likely emerged from an ancestral gene family about 400 million years ago, expanding the diversity of life and programming the development of bone-secreting osteoblast cells. Bone-forming vertebrates now range from the tiny frog Paedophryne amauensis to the mighty blue whale.”

“This study provides a fascinating and compelling example of how the emergence of novel gene regulatory networks connect to new cellular capabilities in the evolutionary process—specifically here in the program of bone formation, ” said Hironori Hojo, lead author and a postdoctoral research associate at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Biology at USC.

“This is a wonderful example of how a narrow focus on the workings of a single gene illuminates bigger questions on the evolution of a skeletal scaffold we mammals share with fish, frogs, lizard and birds, ” said Andrew McMahon, Ph.D., senior author, W.M. Keck Provost Professor and chair of the Department of Stem Cell Research and Regenerative Medicine at the Keck School of Medicine of USC.

As indicated in the news release, “The Sp7 gene encodes a protein known as a transcriptional regulator, which controls the activity of a large number of other osteoblast-specific genes. Since other members of the Sp family regulate gene activity by binding to specific sequences encoded in the DNA, Sp7 was also thought to act this way. However, studies by Hojo and his colleagues demonstrate a very different mechanism. Sp7 partners with another group of transcriptional regulators called the Dlx family and relies on their DNA-binding action to control osteoblast genes.”

Asked about the challenges of doing this study, McMahon told OTW, “Working directly with osteoblasts from the bone presented a technical challenge to obtaining high-quality information on gene regulatory processes. Overturning dogmatic views of how things ‘should’ work was another obstacle.

“We are getting closer to understanding how the key bone-generating cell is made. When we have a more complete understanding, we may be in a position to generate bone de novo where new bone is needed.”