HMGB1 Mediates Macrophage Recruitment and Regional Intervertebral Disc Properties Following Injury
Abstract
Frequently evaluated in musculoskeletal disease, damage associated molecular patterns (DAMPs) respond to tissue damage and cellular stress by facilitating an inflammatory response via macrophage activation and broad inflammatory pathway activation. In the context of disc degeneration (DD), high mobility group box 1 (HMGB1), a potent intracellular DAMP, is seen to be increased within severely degenerated human IVDs and to directly mediate inflammatory responses within disc cells in vitro. To further understand how HMGB1-mediated inflammation influences DD, this study evaluated the possible protective effect of an HMGB1 knockout on DD pathology following injury. Using a needle puncture injury model in murine caudal IVDs, we evaluated DD pathology within an IVD-specific Hmgb1 knockout (KO) model. Structural and compositional changes in IVD cellularity, histopathology, disc height, and biomechanics were evaluated in addition to an assessment of disc inflammation and macrophage presence throughout the course of degeneration. HMGB1 expression robustly increased shortly following needle puncture injury, and elevated levels were sustained up to 28 days post injury both in injured IVDs and in the IVDs adjacent to the level of injury. IVD-specific Hmgb1 KO mice had an increased disc height following injury both at the injured and adjacent to injury levels compared to wild type (WT) control IVDs. Hmgb1 KO also protected against tissue mechanical property losses at both the injured…
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