RESEARCH - New therapeutic hope for degenerative disc disease

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Medscape Rheumatology

Posted 01/18/2007

New Therapeutic Hope for Degenerative Disc Disease

Degenerative disc disease is one of today's most common and costly medical

conditions. Marked by the gradual erosion of cartilage between the

vertebrae, this destructive disease of the spine routinely provokes low back

pain, the leading cause of disability in people under age 45 in the United

States. This condition is also confounding: the factors that account for the

vulnerability of the disc to degeneration and the limited capacity of the

disc for repair remain largely unknown.

For some domestic mammals, including sheep, goats, and dogs, the occurrence

of degenerative disc disease is extremely rare. Intrigued by this fact and

how it might apply to humans, researchers in Toronto, Canada, decided to

conduct a gene expression study on intervertebral discs from canines. Their

results, presented in the December 2006 issue of Arthritis & Rheumatism

http://www.interscience.wiley.com/journal/arthritis, shed light on the

regenerative potential of early embryonic cells within the disc nucleus.

The evolutionary precursor to the backbone, the notochord is a fine,

flexible chord defining the body axis in the early embryos of all

vertebrates. In certain breeds of dogs, notochord cells remain vibrant in

the intervertebral disc into adulthood. Does the degree of biochemical

protection notochord cells provide explain the difference in susceptibility

to degenerative disc disease between canines and humans? For answers, the

researchers examined samples of notochord cells from adult dogs, with

attention to their effect on the regulation of important genes in

chondrocytes, or cells found in cartilage.

What the researchers found was compelling: notochord cells secrete

connective tissue growth factor (CTGF)-a recently characterized protein with

multifunctional anabolic properties. CTGF gene expression was also found in

cell cultures taken from the intervertebral discs of chondrodystrophic

canines-dog breeds closer to humans in musculoskeletal terms. But the

population of notochord cells was much larger in nonchondrodystrophic dogs.

" Our results suggest that nonchondrodystrophic canines are protected against

the development of degenerative disc disease because their discs contain an

abundance of notochord cells that secrete a key anabolic factor, CTGF, "

states the study's senior author, D. Inman, MD, Toronto Western

Research Institute. " These findings provide insight into the biology of the

intervertebral disc, " he further notes, " and raise the possibility of future

novel therapeutic options for this disabling condition. "

But are there notochord cells within the mammalian adult spine? And if they

do, what distinguishes them from spinal tissue? These are among the critical

questions Juergen A. Mollenhauer, PhD, raises in his editorial on the

notochord study. As he observes, the assumption that adult humans do not

possess notochord cells may be biased by the lack of investigations on

healthy human spinal discs. " Taken together, the currently known facts evoke

hopes for a regenerative reservoir, " Dr. Mollenhauer adds, with a firm

emphasis on the need for more research. " Whether notochord cells can be

preserved or reactivated remains to be resolved in the future. "

http://www.medscape.com/viewarticle/550575

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