Summary
Objective
Macrophages are abundantly detected at sites of disc herniation, however, their function
in the disease progression is unclear. We aim to investigate the functions of macrophages
in acute disc herniation using a macrophage Fas-induced apoptosis (MaFIA) transgenic
mouse strain.
Method
To transiently deplete macrophages, a dimerizer, AP20187, or vehicle solution was
administered via intraperitoneal injection to MaFIA mice immediately, day 1 and 2
after annular puncture induced disc herniation. Local infiltrated tissues at disc
hernia and DRGs at corresponding levels were harvested to analyze immune cells and
neuroinflammation on postoperative day (POD) 6 by flow cytometry and/or immunostaining.
Mouse spines were harvested to analyze structures of degenerated discs and adjacent
vertebrae and to assess osteoclast activity by histology and tartrate-resistant acid
phosphatase (TRAP) staining on POD 6, 13, and 20, respectively.
Results
On POD 6, abundant macrophages were confirmed at disc hernia sites. Compared to vehicle
control, AP20187 significantly reduced GFP+ cells in blood, spleen, and local inflammatory tissue. At disc hernia sites, AP20187
markedly reduced macrophages (CD11b+, F4/80+, GFP+CD11b+, CD11b+F4/80+) while increasing neutrophils and B cells. Transient macrophage depletion decreased
ectopic bone formation and osteoclast activity in herniated discs and adjacent cortical
bones for up to 20 days post herniation. Disc herniation elevated expressions of TNF-α,
IL-6, substance P, calcitonin gene-related peptide, accompanied by increasing GFP+, CD11b+ and F4/80+ macrophages. Macrophage depletion did not attenuate these markers of neuroinflammation.
Conclusions
Transient depletion of macrophages altered local inflammatory response at the site
of disc herniation.
Keywords
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Article info
Publication history
Published online: February 06, 2023
Accepted:
January 10,
2023
Received:
May 9,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
