Targeted deletion of the SPARC gene accelerates disc degeneration in the aging mouse

被引:66
作者
Gruber, HE
Sage, EH
Norton, HJ
Funk, S
Ingram, J
Hanley, EN
机构
[1] Carolinas Med Ctr, Dept Orthopaed Surg, Charlotte, NC 28232 USA
[2] Carolinas Med Ctr, Dept Biostat, Charlotte, NC 28232 USA
[3] Virginia Mason, Benaroya Inst, Hope Heart Program, Seattle, WA USA
关键词
intervertebral disc; disc degeneration; matricellular proteins; SPARC;
D O I
10.1369/jhc.5A6687.2005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1131 / 1138
页数:8
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