Intervertebral disc degeneration and ectopic bone formation in apolipoprotein E knockout mice.
Cardiovascular risk factors are known to be associated with intervertebral disc degeneration, but the underlying mechanism is still unclear. The ApoE knockout (KO) mouse is a well-established model for atheroscelorosis. We hypothesized that ApoE is involved in maintaining disc health and that ApoE KO mice will develop early disc degeneration. Discs of ApoE KO and wild-type (WT) mice were characterized with histological/immunological, biochemical, and real-time RT-PCR assays. A comparison of the extracellular matrix production was also performed in disc cells. We demonstrated that ApoE was highly expressed in the endplates of WT discs, and ectopic bone formed in the endplates of ApoE KO discs. Glycosaminoglycan content was decreased in both ApoE KO annulus fibrosus (AF) and nucleus pulposus (NP) cells. Collagen levels were increased in AF and decreased in NP cells. Matrix metalloproteinase-3, -9, and -13 expressions were increased, which may partially explain the impaired matrix production. We also found collagen I, II, aggrecan, and biglycan mRNA expressions were increased in AF cells but decreased in NP cells. Apoptosis was increased in the ApoE KO NP tissue. These results suggest early disc degeneration changes in the ApoE KO mice. ApoE may play a critical role in disc integrity and function.
Department of Orthopedic Surgery, University of Virginia Health System, Charlottesville, VA, USA.
Dawei
D
Zhang
Li
L
Jin
Davis L
DL
Reames
Francis H
FH
Shen
Adam L
AL
Shimer
Xudong
X
Li
D053674:Aggrecans / Q000096:biosynthesis; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D058578:Biglycan / Q000096:biosynthesis; D003094:Collagen / Q000096:biosynthesis; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D007403:Intervertebral Disc / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000503:physiopathology*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D009999:Ossification, Heterotopic / Q000378:metabolism*
D053674:Aggrecans; D001057:Apolipoproteins E; D058578:Biglycan; D016326:Extracellular Matrix Proteins; D003094:Collagen; D020782:Matrix Metalloproteinases