Gene Silencing Directs Muscle-derived Stem Cells To Become Bone-forming Cells

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Gene Silencing Directs Muscle-derived Stem Cells To Become Bone-

forming Cells

http://www.medicalnewstoday.com/medicalnews.php?newsid=44400

Using a relatively new technology called RNA interference to turn off

genes that regulate cell differentiation, University of Pittsburgh

researchers have demonstrated they can increase the propensity of

muscle-derived stem cells (MDSCs) to become bone-forming cells. Based

on these results, the investigators believe that by turning off

specific genetic factors they can control the capacity of MDSCs as a

means of treating various musculoskeletal diseases and injuries.

RNA interference is a simple yet powerful technique that uses short

interfering RNAs (siRNAs) - small molecules that prevent a gene from

being expressed - to turn off the production of specific proteins in

a cell. In their study, the Pitt researchers generated siRNAs to two

mouse genes: MyoD1, a master gene that regulates the formation of

muscle cells or fibers (myogenesis), and Smad6, which encodes a

molecule that specifically inhibits a cell's ability to respond to

bone-forming, or osteogenic, signals.

When the researchers examined cultured cells in which myogenesis was

inhibited, they found a significant increase in the cells' bone-

forming potential. However, contrary to their expectations, the

researchers did not observe any bone formation when the cells were

implanted in skeletal muscle. Yet, when they turned off ostegenic

inhibition in these same cells using Smad6 siRNA prior to implanting

them in mice, 60 percent of the mice developed radiologically

detectable bone within three weeks.

" By understanding the genetic mechanisms that regulate a cell's

propensity to differentiate into one type of cell line over another,

we may be able to regulate their ability to generate bone for the

treatment of various diseases and injuries of the musculoskeletal

system, such as osteoporosis or severe fractures, " said first author

B. Pollett, Ph.D., research associate, department of

orthopaedic surgery, Children's Hospital of Pittsburgh. Corresponding

author ny Huard, Ph.D., the Henry J. Mankin Endowed Chair in

Orthopaedic Surgery Research, University of Pittsburgh School of

Medicine, and Director of the Stem Cell Research Center (SCRC) of

Children's Hospital of Pittsburgh, added that muscle and bone

injuries are very frequent in sports medicine and this research may

someday significantly improve the treatment of such problems.

Others involved in this study include, Tebbets, Bridget M.

Deasy, Ph.D., and Karin A. Corsi of the SCRC of Children s Hospital

of Pittsburgh.

University of Pittsburgh Medical Center

http://www.upmc.edu