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However, the immune mechanisms that may perpetuate CEP damage in MC remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To (i) characterize neutrophils in MC bone marrow and (ii) test whether activated neutrophils can degrade human CEP tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In low back pain patients undergoing lumbar fusion, paired bone marrow aspirates were collected intraoperatively from an MC level and an adjacent non\u2010MC vertebra (intra\u2010patient control). MC neutrophils were characterized by bulk RNA sequencing of sorted CD45\n                      <jats:sup>+<\/jats:sup>\n                      CD66b\n                      <jats:sup>+<\/jats:sup>\n                      cells (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097), flow cytometry (activation (CD66b); neutrophil maturation subsets), and neutrophil elastase (NE) activity in short\u2010term culture supernatants. To model CEP degradation, conditioned media from healthy\u2010donor blood neutrophils incubated \u00b1 neutrophil activator phorbol 12\u2010myristate 13\u2010acetate (PMA) (12.5 or 25 Mio cells\/mL) were applied to human CEP explants (18\u2009h). Proteoglycan loss (sGAG) and collagen loss (hydroxyproline) were quantified as release fractions, normalized to media\u2010only controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MC neutrophils showed an activated, pro\u2010inflammatory transcriptomic signature, including enrichment of calcium\u2010associated processes consistent with degranulation. Flow cytometry demonstrated higher CD66b intensity in MC neutrophils versus intra\u2010patient controls (125.4\u2009\u00b1\u200934.2%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.022) and a trend toward increased band neutrophils (126.7\u2009\u00b1\u200933.4%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.069). NE release was higher in 4\/6 patients (191.2\u2009\u00b1\u2009142.7%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.178) and correlated with band neutrophil abundance (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.67,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.033). PMA activation markedly increased NE activity in conditioned media and was cell\u2010number dependent. CEP exposure to activated neutrophil conditioned media induced significant sGAG release (25 Mio\/mL: 380.1\u2009\u00b1\u2009177.0%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.012; 12.5 Mio\/mL: 123.7\u2009\u00b1\u200922.3%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.048), while hydroxyproline release was not significantly increased.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Neutrophils within MC bone marrow have an activated pro\u2010inflammatory phenotype, and activated neutrophils can degrade CEP proteoglycans ex\u00a0vivo. These findings support a potential immune\u2010mediated mechanism contributing to CEP weakening and indicate that MC are not just reactive changes but themselves have degenerative effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.70170","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T11:02:43Z","timestamp":1773831763000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Modic Change Bone Marrow Neutrophils Are Activated and Degrade Cartilage Endplates"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3064-8364","authenticated-orcid":false,"given":"Irina","family":"Heggli","sequence":"first","affiliation":[{"name":"Center of Experimental Rheumatology, Department of Rheumatology University Hospital Zurich, University of Zurich  Zurich Switzerland"},{"name":"Department of Physical Medicine and Rheumatology Balgrist University Hospital, Balgrist Campus, University of Zurich  Zurich Switzerland"},{"name":"Department of Orthopedics Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Mengis","sequence":"additional","affiliation":[{"name":"Center of Experimental Rheumatology, Department of Rheumatology University Hospital Zurich, University of Zurich  Zurich Switzerland"},{"name":"Department of Physical Medicine and Rheumatology Balgrist University Hospital, Balgrist Campus, University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Devan","sequence":"additional","affiliation":[{"name":"Center of Experimental Rheumatology, Department of Rheumatology University Hospital Zurich, University of Zurich  Zurich Switzerland"},{"name":"Department of Physical Medicine and Rheumatology Balgrist University Hospital, Balgrist Campus, University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Herger","sequence":"additional","affiliation":[{"name":"Center of Experimental Rheumatology, Department of Rheumatology University Hospital Zurich, University of Zurich  Zurich Switzerland"},{"name":"Department of Physical Medicine and Rheumatology Balgrist University Hospital, Balgrist Campus, University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazda","family":"Farshad","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Balgrist University Hospital, University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Habib","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher 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