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A Proinflammatory, Degenerative Organ Culture Model to Simulate Early-Stage Intervertebral Disc Disease.
Published on: February 14, 2021
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Elevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated
Yejia Zhang1,2,3, Zuozhen Tian4, David Gerard5
1Department of Physical Medicine & Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA. yejia.zhang@pennmedicine.upenn.edu.
Scientific Reports
|January 20, 2021
Summary
ADAM8 enzyme activity is high in human degenerative discs. Inactivation of ADAM8 in mice surprisingly increased inflammation and altered collagen, suggesting partial inhibition may treat disc degeneration.
Area of Science:
- Biochemistry
- Molecular Biology
- Orthopedics
Background:
- Elevated ADAM8 enzymatic activity is observed in human degenerative intervertebral discs (IVDs).
- The precise role of ADAM8 in IVD degeneration remains unclear.
Purpose of the Study:
- To investigate the function of ADAM8 in intervertebral disc degeneration using a mouse model.
- To explore the impact of ADAM8 inactivation on inflammatory markers and collagen structure in injured discs.
Main Methods:
- Utilized ADAM8-inactivation mutant mice with impaired self-activation.
- Analyzed gene expression of inflammatory markers (Cxcl1, IL6) and collagen (Col2a1).
- Performed microscopic examination of collagen fiber structure in intact and injured discs using circular polarized light.
Main Results:
- ADAM8 mutant mice showed elevated gene expression of inflammatory markers (Cxcl1, IL6) and type 2 collagen (Col2a1) in injured discs compared to wild-type controls.
- Both mutant and wild-type injured discs exhibited a higher proportion of large collagen fibers than intact discs.
- Intact IVDs from Adam8 mutant mice had a lower proportion of intermediate collagen fibers compared to wild-type.
Conclusions:
- ADAM8 appears to play a regulatory role in inflammation and collagen fiber assembly within the intervertebral disc.
- The findings suggest a complex interaction between ADAM8, inflammation, and tissue repair processes in disc degeneration.
- Partial inhibition of ADAM8 proteolysis may be a more effective therapeutic strategy for intervertebral disc degeneration than complete inactivation.
