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Targeted Deletion of the SPARC Gene Accelerates Disc Degeneration in the Aging Mouse

Helen E. Gruber, E. Helene Sage, H. James Norton, Sarah Funk, Jane Ingram and Edward N. Hanley, Jr.

Department of Orthopaedic Surgery (HEG,JI,ENH) and Department of Biostatistics (HJN), Carolinas Medical Center, Charlotte, North Carolina, and Hope Heart Program, The Benaroya Institute at Virginia Mason, Seattle, Washington (EHS,SF)

Correspondence to: Helen E. Gruber, PhD, Director, Orthopaedic Research Biology, Cannon Bldg., 3rd Floor, Carolinas Medical Center, PO Box 32861, Charlotte, NC 28232. E-mail: helen.gruber{at}carolinashealthcare.org

SPARC (secreted protein, acidic, and rich in cysteine) is a matricellular protein that is present in the intervertebral disc; in man, levels of SPARC decrease with aging and degeneration. In this study, we asked whether targeted deletion of SPARC in the mouse influenced disc morphology. SPARC-null and wild-type (WT) mice were studied at 0.3–21 months of age. Radiologic examination of spines from 2-month-old SPARC-null mice revealed wedging, endplate calcification, and sclerosis, features absent in age-matched WT spines. Discs from 3-month-old SPARC-null mice had a greater number of annulus cells than those of WT animals (1884.6 ± 397.9 [mean ± SD] vs 1500.2 ± 188.2, p=0.031). By 19 months discs from SPARC-null mice contained fewer cells than WT counterparts (1383.6 ± 363.3 vs 1466.8 ± 148.0, p=0.033). Histology of midsagittal spines showed herniations of lower lumbar discs of SPARC-null mice ages 14–19 months; in contrast, no herniations were seen in WT age-matched animals. Ultrastructural studies showed uniform collagen fibril diameters in the WT annulus, whereas in SPARC-null disc fibrils were of variable size with irregular margins. Consistent with the connective tissue deficits observed in other tissues of SPARC-null mice, our findings support a fundamental role for SPARC in the production, assembly, or maintenance of the disc extracellular matrix.

(J Histochem Cytochem 53:1131–1138, 2005)

Key Words: intervertebral disc • disc degeneration • matricellular proteins • SPARC

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