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Intervertebral disc degeneration and ectopic bone formation in apolipoprotein E knockout mice
Dawei Zhang1, Li Jin, Davis L Reames
1Department of Orthopedic Surgery, University of Virginia Health System, Charlottesville, VA, USA.
Summary
Apolipoprotein E (ApoE) deficiency in mice leads to early intervertebral disc degeneration, indicated by altered matrix composition and increased cell death. These findings highlight ApoE's critical role in maintaining spinal disc health.
Area of Science:
- Biomedical research
- Orthopedics
- Genetics
Background:
- Cardiovascular risk factors are linked to intervertebral disc degeneration (IVDD).
- The precise mechanisms connecting these conditions remain largely unknown.
- Apolipoprotein E (ApoE) knockout (KO) mice serve as a model for atherosclerosis.
Purpose of the Study:
- To investigate the role of ApoE in intervertebral disc health.
- To determine if ApoE deficiency accelerates disc degeneration.
- To elucidate the molecular and cellular changes in the intervertebral discs of ApoE KO mice.
Main Methods:
- Histological and immunological analysis of mouse intervertebral discs.
- Biochemical assays to assess extracellular matrix components.
- Real-time reverse transcription polymerase chain reaction (RT-PCR) for gene expression analysis.
- Comparison of extracellular matrix production in isolated disc cells.
Main Results:
- ApoE expression was detected in the endplates of wild-type (WT) discs; ectopic bone formation occurred in ApoE KO discs.
- Decreased glycosaminoglycan and altered collagen levels were observed in ApoE KO annulus fibrosus (AF) and nucleus pulposus (NP) cells.
- Increased expression of matrix metalloproteinases (MMPs) -3, -9, and -13 was noted in ApoE KO discs.
- Differential mRNA expression of collagen I, II, aggrecan, and biglycan in AF and NP cells of ApoE KO mice.
- Elevated apoptosis in the NP tissue of ApoE KO mice.
Conclusions:
- ApoE deficiency in mice results in early signs of intervertebral disc degeneration.
- ApoE appears to play a crucial role in maintaining the structural integrity and function of spinal discs.
- These findings suggest a potential link between cardiovascular health and spinal disc degeneration mediated by ApoE.
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