Modic Change Bone Marrow Neutrophils Are Activated and Degrade Cartilage Endplates

作者：Irina Heggli, Tamara Mengis, Ján Deván, Nick Herger, Mazda Farshad, M. Farhan Habib, Christopher P. Ames, Oliver Distler, Aaron J. Fields, Stefan Dudli · 发表于：JOR Spine · 年份：2026 · DOI：10.1002/jsp2.70170 · 被引用次数：3 · 研究领域：Immune cells in cancer、Immune Response and Inflammation、Bone and Joint Diseases

ABSTRACT Background Vertebral endplate bone marrow lesions (Modic changes, MC) are linked to vertebrogenic pain and to structural defects of the bony and cartilaginous endplates (CEP). However, the immune mechanisms that may perpetuate CEP damage in MC remain unclear. Objective To (i) characterize neutrophils in MC bone marrow and (ii) test whether activated neutrophils can degrade human CEP tissue. Methods In low back pain patients undergoing lumbar fusion, paired bone marrow aspirates were collected intraoperatively from an MC level and an adjacent non‐MC vertebra (intra‐patient control). MC neutrophils were characterized by bulk RNA sequencing of sorted CD45 + CD66b + cells ( n = 7), flow cytometry (activation (CD66b); neutrophil maturation subsets), and neutrophil elastase (NE) activity in short‐term culture supernatants. To model CEP degradation, conditioned media from healthy‐donor blood neutrophils incubated ± neutrophil activator phorbol 12‐myristate 13‐acetate (PMA) (12.5 or 25 Mio cells/mL) were applied to human CEP explants (18 h). Proteoglycan loss (sGAG) and collagen loss (hydroxyproline) were quantified as release fractions, normalized to media‐only controls. Results MC neutrophils showed an activated, pro‐inflammatory transcriptomic signature, including enrichment of calcium‐associated processes consistent with degranulation. Flow cytometry demonstrated higher CD66b intensity in MC neutrophils versus intra‐patient controls (125.4 ± 34.2%, p = 0.022) and a trend...