Targeted deletion of the SPARC gene accelerates disc degeneration in the aging mouse.
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.
Gruber
Helen E
HE
Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, NC 28232, USA. helen.gruber@carolinashealthcare.org
Sage
E Helene
EH
Norton
H James
HJ
Funk
Sarah
S
Ingram
Jane
J
Hanley
Edward N
EN
D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000473:pathology; D024022:Fibrillar Collagens / Q000648:ultrastructure; D006547:Hernia / Q000000981:diagnostic imaging / Q000473:pathology; D007403:Intervertebral Disc / Q000000981:diagnostic imaging / Q000473:pathology* / Q000648:ultrastructure; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015676:Osteonectin / Q000235:genetics / Q000502:physiology*; D011859:Radiography; D012598:Sclerosis / Q000000981:diagnostic imaging / Q000473:pathology; D013997:Time Factors
D024022:Fibrillar Collagens; D015676:Osteonectin