Sci. Aging Knowl. Environ., 2 July 2003
Vol. 2003, Issue 26, p. nw94
[DOI: 10.1126/sageke.2003.26.nw94]

NOTEWORTHY ARTICLES

Talkin' 'Bout Regeneration

Researchers finger muscle-making cells

Mitch Leslie

http://sageke.sciencemag.org/cgi/content/full/sageke;2003/26/nw94

Key Words: somite • myogenic • myoblast • Myf5nLacZ • {beta}-catenin

Even gym rats grow weaker in old age, as their muscles lose the capacity to repair the damage caused by working out and even walking. A new study identifies the stem cells that replenish damaged muscle and reveals the signaling pathway that spurs these cells to specialize. The discovery could eventually lead to treatments that boost strength in the elderly and in patients with muscle-wasting diseases.

Our muscles are constantly refurbishing themselves. This capacity is vital, says Ronald Cohn, a pediatrician and geneticist at Johns Hopkins Hospital in Baltimore, Maryland. "Every time we walk, run, or exercise, we have muscle damage." The ability to make fresh cells to supplant injured ones falters in old age and in diseases such as muscular dystrophy. Several kinds of muscle precursor cells might give rise to the replacements. Stem cell biologist Michael Rudnicki of the Ottawa Health Research Institute in Ontario, Canada, and colleagues suspected ones that carry a marker protein on their surface called CD45. If injected into the blood, these cells migrate to the muscles and start dividing, but nobody knew whether CD45 cells that naturally reside within muscle also spark regeneration.

To find out, Rudnicki's team injured leg muscles of mice with an injection of cobra venom. The number of CD45 cells within the muscle increased 10-fold after the damage. The researchers also engineered mice to produce a chemical marker in cells that had roused a gene known to be involved in the early stages of muscle specialization. None of the CD45-labeled cells made the chemical before the injury, but about 7% did by 4 days afterward, suggesting that the insult urged some CD45 cells to become muscle. A family of molecules called Wnt proteins stimulates muscle formation during embryonic development; the researchers wanted to determine whether the same proteins galvanize regeneration in adults. So they injected two molecules that thwart Wnt proteins into mice that were recovering from muscle injuries. The treatment restrained the rise in number of CD45-toting cells and slashed the number of cells that were starting to specialize. Together, the results suggest that CD45 cells spawn new muscle and that Wnt proteins kick-start the process, says Rudnicki.

"The paper is very important for the field," says muscle cell biologist Stephen Tapscott of the Fred Hutchinson Cancer Research Center in Seattle, Washington. It nails down the function of the CD45 cells and shows that the same signals orchestrate embryonic muscle development and adult healing. Nobody knows why muscle repair breaks down in older folks, but CD45-carrying cells don't vanish when we hit 40, says Rudnicki. If faulty Wnt signaling is the culprit, restoring it could help strengthen seniors and people with muscle-weakening diseases, says Cohn. Even if Wnt proteins don't go haywire as we age, tweaking the pathway might help rebuild slack muscles, he adds. More work should reveal whether Wnt-based therapies will bulk up lab mice or even gym rats.

--Mitch Leslie; suggested by Greg Liszt


July 2, 2003
  1. A. Polesskaya, P. Seale, M. A. Rudnicki, Wnt signaling induces the myogenic specification of resident CD45+ adult stem cells during muscle regeneration. Cell 113, 841-852 (2003). [Abstract] [Full Text] [CrossRef][Medline]
Citation: M. Leslie, Talkin' 'Bout Regeneration. Sci. SAGE KE 2003, nw94 (2 July 2003)
http://sageke.sciencemag.org/cgi/content/full/sageke;2003/26/nw94








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