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Age-Related Changes in Fibromodulin and Lumican in Human Intervertebral Discs

Sztrolovics, Robert, PhD*; Alini, Mauro, PhD; Mort, John S., PhD*; Roughley, Peter J., PhD

Basic Science
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SDC

Study Design. An analysis of proteoglycans of the intervertebral disc using immunoblotting of tissue extracts.

Objectives. To investigate the changes in structure and abundance of fibromodulin and lumican in human intervertebral discs during aging and degeneration.

Summary of Background Data. Fibromodulin and lumican are keratan sulfate proteoglycan constituents of the disc’s extracellular matrix, whose interaction with collagen fibrils may contribute to the mechanical properties of the tissue. Changes in their abundance and/or structure that occur with aging and degeneration therefore may have an impact on disc function.

Methods. Lumbar intervertebral discs were obtained from individuals of different ages, and extracts of anulus fibrosus and nucleus pulposus were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using antibodies specific for fibromodulin and lumican.

Results. The major changes in abundance observed with age were a decrease in fibromodulin in the adult nucleus pulposus and an increase in lumican in anulus fibrosus during early juvenile development. In addition, fibromodulin in the anulus fibrosus exhibited a structural change with increasing age, characterized by a shift toward the predominance of its glycoprotein form lacking keratan sulfate. Fibromodulin was more abundant in the anulus fibrosus than in nucleus pulposus at all ages, whereas lumican was much more abundant in nucleus pulposus than in anulus fibrosus in the young juvenile; in the adult, however, lumican was present in comparable levels in both tissues. With increasing degrees of degeneration, fibromodulin exhibited an increase in abundance.

Conclusions. Growth, aging, and degeneration of the intervertebral disc are associated with changes in the abundance and structure of fibromodulin and lumican, which presumably influence the functional properties of the tissue.

From the *Joint Diseases Laboratory, Shriners Hospital for children, the †Orthopaedic Research Laboratory, Royal Victoria Hospital, and the ‡Genetics Unit, Shriners Hospital for Children, and Division of Surgical Research, Deptartment of Surgery, McGill University, Montreal, Quebec, Canada.

Supported in part by the Arthritis Society of Canada and the Shriners of North America.

Acknowledgment date: February 18, 1998.

First revision date: May 29, 1998.

Second revision date: November 10, 1998.

Acceptance date: December 8, 1998.

Address reprint requests to

Peter J. Roughley, PhD

Genetics Unit, Shriners Hospital for Children

1529 Cedar Avenue

Montreal, Quebec H3G 1A6

Canada

E-mail:proughley@shriners.mcgill.ca

Device status category: 1.

© 1999 by Lippincott Williams & Wilkins