Master Gene Makes Skeletal Progenitor Cells Differentiate Into Cartilage Cells

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Master Gene Makes Skeletal Progenitor Cells Differentiate Into

Cartilage Cells

http://www.sciencedaily.com/releases/2006/11/061127210600.htm

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. n

Lee, associate professor of molecular and human genetics at BCM,

director of the Skeletal Dysplasia Clinic at Texas Children's

Hospital and a 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.

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. "

Working in a genetic lab allowed Lee and his colleagues to learn

from gene-caused diseases of the skeletal system. Studies of human

tissues proved that the protein activity identified in cells in the

laboratory and in studies with mice occurred in humans as well.

Others who took part in the research include Drs. Guang Zhou, Qiping

Zheng, Feyza Engin, Elda Munivez, and Yuqing Chen of Baylor College

of Medicine; Eiman Sebald of Cedars Sinai Medical Center in Los

Angeles; and Deborah Krakow of the Geffen School of Medicine,

University of California, Los Angeles.

Funding for this research came from the National Institutes of

Health and the Baylor College of Medicine Mental Retardation and

Development Disability Research Center.