Skeletal progenitor cells differentiate into cartilage cells when one master gene actually suppresses the action of another, said Baylor College of Medicine researchers in a report that appears online in the journal Proceedings of the National Academy of Sciences.
Skeletons are made of bone and cartilage cells that are differentiated from the same multipotent stem cell, said Dr. Brendan Lee, associate professor of molecular and human genetics at BCM, director of the Skeletal Dysplasia Clinic at Texas Children’s Hospital and a Howard Hughes Medical Institute investigator. This same stem cell gives rise to bone, cartilage, fat and fibroblasts.
“The big question is what are the master genes that make a stem cell go one way versus another,” said Lee.
Both SOX9 and RUNX2 are master transcription factors involved in the process of differentiating bone and cartilage.
SOX9 and RUNX2 are obvious candidates for drug development. A drug that could block SOX9 would probably cause skeletal progenitor cells to become bone cells. That'd be handy for bone repair and bone restoration for people suffering osteoporosis. A drug that could turn on SOX9 could produce cartilage to replace aged or damaged cartilage.
The master protein SOX9 directs skeletal progenitor cells to become cartilage and another master protein, RUNX2, directs such cells to become bone, However, he said, the primordial skeletal cell has both RUNX2 AND SOX9.
“We then asked a simple question: Could these master transcription factors (that direct the expression of other genes) directly affect one another’s function"” he said. After studies in the laboratory, with mice and with humans, the answer was yes.
“SOX9 appears to be the dominant player,” said Lee. “When it is present in a progenitor cell, it turns off RUNX2 and allows the cell to become cartilage.”
That does not answer the question of how such cells become bone.
“Clearly, something must turn off SOX9,” said Lee. “That’s the next question we have to answer.”
These two genes are part of a much larger set of genes that control cell differentiation (i.e. the process by which cells turn into all the specialized cell types on the body). Advances in biotechnology are accelerating the rate at which scientists working in labs can figure out how all these genes work. The more they learn the better able they will be to intervene and turn cells into any types needed for repair and rejuvenation.
Here's the paper: Dominance of SOX9 function over RUNX2 during skeletogenesis.
|Share |||Randall Parker, 2006 December 03 11:51 AM Biotech Stem Cells|